Protected: OCULAR 200:1 – COMING SOON!
November 18, 2023
CERAMIDE BLOCKER 200:1 – Lipotoxicity Neutralizer – WORLD WIDE LAUNCH DATE APRIL 15th!
February 9, 2024
TRIGLYCERIDE DECIMATOR 200:1 – Coming Soon!
INTRODUCING
INTERSTELLAR BLEND™
triglyceride
DECIMATOR
200:1 Concentration
scienTIFIC EVIDENCE
Lowering triglycerides can have several effects on obesity
1. Improved lipid metabolism: Obesity is often associated with dyslipidemia, which is characterized by elevated levels of triglycerides in the blood. Lowering triglyceride levels can help restore normal lipid metabolism, reducing the risk of obesity-related complications such as cardiovascular diseases and liver steatosis.
2. Reduced fat accumulation: High levels of triglycerides can contribute to the accumulation of fat in adipose tissue and other organs. By lowering triglyceride levels, the body is less likely to store excess fat, which can help prevent further weight gain and promote weight loss.
3. Enhanced insulin sensitivity: Obesity is closely linked to insulin resistance, a condition in which cells become less responsive to the effects of insulin. Elevated triglyceride levels can impair insulin signaling and worsen insulin resistance. Lowering triglycerides can improve insulin sensitivity, allowing for better glucose uptake and utilization by cells, which can help manage obesity and prevent the development of type 2 diabetes.
4. Reduced inflammation: Obesity is associated with chronic low-grade inflammation, which can contribute to the development of metabolic disorders. Elevated triglyceride levels can promote inflammation in adipose tissue and other organs. Lowering triglycerides can help reduce inflammation, potentially improving metabolic health and reducing obesity-related complications.
It is important to note that while lowering triglycerides can have beneficial effects on obesity, it is just one aspect of a comprehensive approach to managing and treating obesity. Lifestyle modifications, including a healthy diet, regular physical activity, and weight management, are also crucial for long-term success in managing obesity.
Methods: This was an observational study using data from the National Health and Nutrition Examination Survey (2005–2018), a cross-sectional and nationally representative database. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). TyG index was calculated based on the equation as follows: ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2], and participants were divided into quartiles based on TyG index. Weighted multivariable logistic regression models were used to explore the relationship between the TyG index and depression.
Results: A total of 13,350 patients were included, involving 1001 (7.50%) individuals with depression. Higher TyG index is significantly associated with elevated depressive symptoms in U.S. adults. Multivariate-adjusted HRs for patients in the TyG index 4th quartile were higher for depression (OR = 1.46; 95% confidence interval (CI) 1.30, 1.64) compared with the 1st quartile of TyG index. Similar results were seen in men and women, across age groups, and baseline comorbidities.
Conclusion: In this large cross-sectional study, our result suggests that population with higher TyG index are significantly more likely to have depressive symptoms in U.S. adults.
Obesity-Related Changes in High-Density Lipoprotein Metabolism and Function
In obese individuals, atherogenic dyslipidemia is a very common and important factor in the increased risk of cardiovascular disease. Adiposity-associated dyslipidemia is characterized by low high-density lipoprotein cholesterol (HDL-C) levels and an increase in triglyceride-rich lipoproteins. Several factors and mechanisms are involved in lowering HDL-C levels in the obese state and HDL quantity and quality is closely related to adiponectin levels and the bioactive lipid sphingosine-1-phosphate.
Recent studies have shown that obesity profoundly alters HDL metabolism, resulting in altered HDL subclass distribution, composition, and function. Importantly, weight loss through gastric bypass surgery and Mediterranean diet, especially when enriched with virgin olive oil, is associated with increased HDL-C levels and significantly improved metrics of HDL function. A thorough understanding of the underlying mechanisms is crucial for a better understanding of the impact of obesity on lipoprotein metabolism and for the development of appropriate therapeutic approaches. The objective of this review article was to summarize the newly identified changes in the metabolism, composition, and function of HDL in obesity and to discuss possible pathophysiological consequences.
Postulated effects of obesity on adiponectin and HDL metabolism. In normal-weight subjects, adipocytes produce adiponectin, which enhances expression of the ATP-binding cassette transporter A1 (ABCA1) through activation of peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα), leading to HDL assembly. Further, adiponectin increases the hepatic production of apoA-I. During the state of obesity, adipocytes manifest several altered properties, which play a role in the reduction of HDL-C. Increased inflammation and fat accumulation in the adipocytes reduces the production of adiponectin and impairs cholesterol flux to HDL. The reduction of adiponectin downregulates apoA-I production and ABCA1 expression in hepatocytes, thus reducing HDL assembly.
Metabolic syndrome (MetS), also known as syndrome X, ‘insulin resistance syndrome’, and hypertriglyceridemic waist, is a clustering of obesity, hyperglycemia, insulin resistance, and dyslipidemia. MetS increases the risk of developing atherosclerotic cardiovascular disease (CVD) and is now considered one of the most important cardiovascular risk factors.
ingredients
13-oxo-9,11-octadecadienoic acid
In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitroexperiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic Triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
3,5,6,7,8,3′,4′-heptamethoxyflavone
Oil Red O staining was used to observe the accumulation of lipids and foam cell formation. As shown in Figure 3A, the number of red lipid droplets was significantly increased, and the lipid droplets were distributed in a ring-like pattern within the ox-LDL-induced RAW264.7 cells, which indicated that the foam cell model was successfully established. Incubation with TAN, HxMF, and HpMF significantly reversed such consequences. In addition, the contents of Triglyceride and TC were quantitatively tested. As expected, the levels of Triglyceride and TC were significantly increased by ox-LDL stimulation (Figures 3B,C). TAN (12, 25, and 50 μM) significantly reduced Triglyceride levels in a dose-dependent manner. The Triglyceride content was significantly reduced by HxMF (25 and 50 μM) and HpMF (50 μM) treatments. All three PMFs showed significant inhibition of TC levels in ox-LDL-induced RAW264.7 cells.
6-Gingerol
Excessive synthesis of Triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited Triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay.
Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than Triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic Triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.
We investigated the effects of 6-gingerol on adiposity and obesity-induced inflammation by focusing on the regulation of adipogenesis and adipokines in white adipose tissue (WAT) of diet-induced obese mice. C57BL/6 mice were fed a high-fat diet (HFD) containing 0.05% 6-gingerol for 8 weeks. 6-Gingerol supplementation significantly reduced body weight, WAT mass, serum Triglyceride , leptin and insulin levels, and HOMA-IR in HFD-fed mice.
Additionally, the size of adipocytes in epididymal fat pads was reduced in HFD-fed mice by 6-gingerol supplementation. 6-Gingerol reduced the mRNA and protein levels of adipogenesis-related transcription factors, such as SREBP-1, PPARγ, and C/EBPα in WAT. Furthermore, 6-gingerol suppressed the expression of lipogenesis-related genes, such as fatty acid synthase and CD36 in WAT. Adiponectin expression was significantly increased, whereas inflammatory adipokines (leptin, resistin, TNF-α, MCP-1, and PAI-1) and the macrophage marker F4/80 were significantly reduced in the WAT of HFD-fed mice by 6-gingerol supplementation. In conclusion, 6-gingerol effectively contributed to the alleviation of adiposity and inflammation in WAT, which is associated with the regulation of adipokines in diet-induced obese mice.
9-oxo-10(E),12(E)-octadecadienoic acid
Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo.
In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic Triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
Acacia senegal Seeds
Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), Triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed.
Apart from reduced atherosclerotic plaques in aorta () and increased lumen volume (), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, Triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics.
Effect of Gum Arabic (Acacia senegal, L. Willd) on lipid profile and performance of Laying Hens
Objective: This experiment studied effect of Gum Arabic as a supplementary diet and its effect on lipid profile (serum, egg yolk and meat) and performance of Laying Hen. Methodology and results: One hundred and fifty commercial laying hens (29 weeks age/ white lohmann) were used. The 150 laying hens are divided into five groups randomly G1, G2, G3, G4 and G5, where each group contained 30 laying hens kept in separated battery house. G1(Control) was fed basal layers diet while G2, G3, G4 and G5 were fed basal diet supplemented with Gum Arabic concentration at 1, 3, 5 and 7% respectively. The study revealed that in serum, there was a significant decrease in cholesterol, Triglyceride , but no significant difference in High Density protein (HDP) – cholesterol at P≤ 0.05, in egg yolk.
There was a significant decrease in cholesterol for G5 compared with G1, also there was a significant decrease Triglyceride in G4 and G5 compared with G1 indicated that there was a decrease in phospholipids in G5 compared with G1. Lipid profile of meat for treated groups (G2, G3, G4 and G5) showed no significant difference at P≤ 0.05 compared with non- treated group (G1). The performance (body weight, egg weight and daily egg production) of laying hens showed significant increase at P≤ 0.05, but there was an increase in body and egg weight. Finally, there was no significant difference in daily egg production at P≤ 0.05. The addition of Gum Arabic as supplement of laying hens diet indicated there was no significant difference in serum cholesterol and daily egg production. Whereas, it is showed significant decrease in Triglyceride , total lipid and phospholipids, but indicated significant increase in egg and body weight. Application of Gum Arabic as supplement in the diet of poultry production should be done because Gum Arabic is rich in highly soluble fiber.
The prevailing strategy for the management of hypercholesterolemia is the use of HMG-CoA reductase inhibitors which work by inhibiting cholesterol synthesis by HMG-CoA reductase in the liver and removal of excess cholesterol level in peripheral circulation by several mechanisms of reverse cholesterol transport [47, 48]. Excess cholesterol in the circulatory system is indicated by biomarker indices of dyslipidaemia and abnormal lipoproteins ratios, which can be regulated by proper fractional esterication of cholesterol and reverse cholesterol transport (RCT) [49, 50]. Cholesterol present in the intestine is rst absorbed in the form of chylomicron (Triglyceride rich complex) and is then modied and packaged as high-density lipoprotein (HDL) cholesterol. Therefore, the ratio of Triglyceride to HDL is indicative of the levels of peripheral cholesterol in circulation.
Abnormal cholesterol esterication rates in apoB-lipoprotein- depleted plasma (fractional esterication) and lipoprotein particle size result in dyslipidaemia [49, 51]. In animal model, specically hypercholesteraemic rabbits, exhibit elevated levels of the biomarker indices of dyslipidaemia, such as the logarithm of the TG/HDL ratio, total cholesterol/ HDL (Castelli risk index -I (CRI-I)) and LDL-cholesterol/HDL-cholesterol (Castelli risk index-II (CRI-II)). In the present study, the treatment of hypercholesterolemic rabbits with an aqueous seed extract of Acacia senegal (L.) Willd. caused a signicant reduction in the atherogenic index and CRI – I&II, indicating improved fractional esterication of cholesterol and reverse cholesterol transport.
Achillea millefolium L.extract
Background: Recent studies have reported that herbal extracts may have some protectiveeffect against the complications of diabetes mellitus. This study aimed to investigate theeffects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage,lipid abnormality, and glycemic control in diabetic rats.
Methods: Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and theirserum samples were separated in order to measurebloodglucose,serum total protein,lipids, and liver enzymes.
Results: There was a significant reduction inbloodglucose,serum liver enzymes, Triglycerides , and total- andLDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterolserum level in the Achillea millefolium-treated groups.
Conclusion: Achillea millefolium extract compared to metformin reduceslipid abnormality,bloodglucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Background: Recent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats.
Methods: Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes.
Results: There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Conclusion:Achillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.
Achillea sibirca extract
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Acorus calamus L.extract
Hypolipidemic Effect of Methanol Fraction of Acorus calamus Linn. in Diet-Induced Obese Rats
Acorus calamus Linn. is a traditional medicinal plant included in “lekhaneyagana” (which means “reduce excess fat”), a pharmacological classification mentioned by Charaka in Charakasamhita. Traditionally, this plant has been prescribed as a first-line treatment for many ailments such as digestive problems, diabetes, obesity, and related problems. The purpose of the present study was to check the effect of methanolic fraction of A. calamus on serum lipids, Lecithin-cholesterol acyltransferase (LCAT) enzyme, and apolipoproteins.
We found that treatment of A. calamus at concentrations of 200 and 400 mg/kg body weight was able to reduce total cholesterol (T-c), Triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) levels and increase high-density lipoprotein cholesterol (HDL-c) levels compared to model control group. A. calamus treatment results in activation of LCAT enzyme, which helps in the maturation of HDL-c. ApoA1 level was found to be increased considerably by the administration of A. calamus extract, and the Apo B level was decreased. GCMS analysis of the A. calamus extract showed the presence of compound, Friedelan-3-one. The result suggests the use of methanol fraction of A .calamus, as a potential drug for controlling the cholesterol level.
Agaricus blazei Mur ill extract
This study was performed to investigate the effects of liquid culture of Agaricus blazei on the lipid metabolism and enzyme activities in growing male rats. Sprague-Dawley rats were given four different types of diets for a succeeding period of 5 weeks, respectively a normal diet group (7% corn oil), a high fat diet group (7% com oil + 15% lard), a 20 or 30% Agaricus diet groups (high fat diet + 20 or 30% Agaricus in water) according to the levels of Agaricus supplementation. The body weight gains, food intake, food efficiency ratios, and hepatic, kidney, spleen and pancreas weights of the rats fed 20 or 30% Agaricus diets were similar to those of the rats fed high fat diet. The epididymal fat pad weight of the rats fed high fat diet and 20 or 30% Agaricus diets were significantly higher than that of the rats fed normal diet.
The concentrations of serum Triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol, and the activity of glutamic pyruvic transaminase in the rats fed 30% Agaricus diet were significantly lower than those in the rats 114 high fat diet. But the concentrations of hepatic total cholesterol and Triglyceride of rats fed the 20 or 30% Agaricus diets were similar to those of rats fed the high fat diet. The HDL-oholesterol/total-cholesterol ratio of the rat fed 30% Agaricus diet was significantly higher than that of the rats fed high fat diet, The activity of glutamic oxaloacetic transaminase in the rats fed 20 or 30% Agaricus diets were similar to those in the rats fed high fat diet. There were no differences in the concentrations of total protein, hemoglobin and glucose, and the activities of alkaline phosphatase, and the atherogenic index in the serum among the experimental groups. These results showed that the 30% Agaricus diet feeding decreased the total cholesterol, the Triglyceride and the LDL-cholesterol, and increased the HDL-oholesterol/total cholesterol ratio in serum of rats.
Obesity and diabetes mellitus are associated with common pathogenic mechanism, and ${\beta}-glucan$ of Agaricus blazei Murill is potent inhibitor of intestinal ${\alpha}-glycosidase$ and inhibit the digestion of starch and sucrose in the small intestine. In this studies, there was observed the anti-hyperglycemic effect in obese diabetic mice(C57BLKsJ db/db), which were supplied Agaricus and Acarbose for 5 weeks. In db/db mice, food intake and body weight gain were decreased significantly in Agaricus groups(p<0.05). Also these group exhibited lower fasting serum glucose level compared with control group. HbA1c level, Triglyceride level, total cholesterol level, HDL cholesterol level, LDL cholesterol level and VLDL cholesterol level were lowered in db/db mice. The activity of disaccharidases on proximal and distal segments of small intestine was decreased. In conclusion, it was assumed that ${\beta}-glucan$ of Agaricus blazei Murill has anti-hyperglycemic and anti-obesitic effects by reducing food intake and body weight gain, and also decreasing serum glucose and lipid level through inhibiting the activity of small intestinal disaccharidases.
Ajuga iva extract
Diabetes is also associated with hyperlipidaemia (i.e. high levels of plasma total cholesterol, LDL-C and triglycerides and low plasma HDL-C)[33] which plays an important role in the development of premature atherosclerosis. Indeed, in STZ-induced diabetic rats, a significant increase of serum LDL-C and very-low-density lipoprotein (VLDL)-C and reduction in HDL-C compared with normal control rats were noted.[34] High total cholesterol level is one of the major risk factors for coronary heart diseases,[35] constituting the main cause of morbi-mortality in diabetes mellitus.[36]
The present study was designed to explore the possible antioxidant and hypolipidemic effects of the aqueous extract of Ajuga iva (0.5% in the diet) in rats fed a high-cholesterol (1%) diet (HCD). The results indicated that the HCD-Ai versus HCD treatment led to many changes in biochemical parameters. They showed a decrease of plasma total cholesterol (TC) and VLDL-cholesterol but an increase of HDL2-cholesterol. The triacylglycerol contents were reduced in plasma and in VLDL. The lipid peroxidation determined by TBARS was decreased by 75% in plasma. TBARS in liver, heart and kidneys were highly reduced excepted in the adipose tissue. Ajuga iva treatment enhanced superoxide dismutase activity in liver and kidney.
Glutathione reductase activity was lowered in adipose tissue but increased in liver and in kidney. A significant increase was noted in glutathione peroxidase activity in liver, heart and kidney but a low value in adipose tissue was observed. In conclusion, the present study demonstrates that in addition to its potent triglyceride and TC-lowering effects, Ajuga iva is effective in improving the antioxidant status by reducing lipid peroxidation in plasma and tissues and enhancing the antioxidant enzymes in rats fed high-cholesterol diet. Furthermore, Ajuga iva may reduce intestinal cholesterol absorption.
Alfalfa extract Total Flavonoids
The two last groups orally received aqueous extract of alfalfa for 21 days. At the end of experiment, sugar, cholesterol, Triglycerides, high-density and low-density lipoprotein, and aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were measured in the samples. Consumption of aqueous alfalfa extract significantly reduced glucose, cholesterol, Triglycerides, and low-density lipoprotein (LDL) levels in the diabetic rats but enhanced high-density lipoprotein (HDL) levels. ALT and AST liver enzyme levels were also reduced in blood. Histological examination showed that the aqueous alfalfa extract caused reconstruction of damaged liver and enhanced Langerhans islets’ diameter in pancreas. Therefore, all signs of diabetes were improved by oral administration of alfalfa in defined dose.
Alisma orientalis (Sam.) Juzep.extract
Alisma orientale (Sam.) Juzep (A. orientale) is a traditional herb that is often used to treat disease including edema and hyperlipidemia. However, the molecular mechanism by which Alisma orientale (Sam.) Juzep exerts itshypolipidemiceffects remains unclear. In this study, a diabetic rat model was established by feeding ahigh-fat andhigh-sugardiet combined with a low-dose streptozotocin injection (HFS). Then the rats were treated with an A. orientale water extract (AOW), an A. orientale ethanolic extract (AOE) or metform (MET). The gut microflora and liver transcriptome were analyzed byhigh-throughput next-generation sequencing. Ultra-performance liquid chromatography-triple quadrupole-mass spectrometry was employed to analyze the major compounds in the AOE. The results showed that theserum totalcholesterol (TC) and low density lipoproteincholesterol (LDL-C) levels in rats of the AOE group (2.10 g/kg/day, 14 days) were significantly lower than those in the HFS group (p<0.01).
Moreover, AOE treatment altered the gut microecology, particularly modulating the relative abundance of gut microflora involved inlipidmetabolism compared with the HFS group. Furthermore, compared with the HFS group, the mRNA expression levels of Fam13a, Mapk7, Mpp7, Chac1, Insig1, Mcpt10, Noct, Greb1l, Fabp12 and Hba-a3 were upregulated after the administration of AOE. In contrast, the mRNA expression levels of Lox, Mybl1, Arrdc3, Cyp4a2, Krt20, Vxn, Ggt1, Nr1d1 and S100a9 were downregulated. Moreover, AOE treatment for two weeks markedly promoted the relative abundance of Lachnospiraceae (p = 0.0013). The triterpenoids contents in AOE were alisol A, alisol A 24-acetate, alisol B, alisol B 23-acetate, alisol C 23-acetate, alisol F, alisol F 24-acetate, and alisol G. Our findings above illustrated that thehypolipidemiceffect of the triterpenoids of A. orientale is mediated mainly through alteration of the gut microecology and the regulation of genes involved incholesterolmetabolism, especially Insig1.
Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging hepatic manifestation of metabolic syndrome. However, its unrevealed mechanism and complicated comorbidities have led to no specific medication, except for weight loss and lifestyle modification. Alisma orientale (Sam.) Juzep (A. orientale, Alismataceae) has been increasingly reported on therapeutic effects of A. orientale against NAFLD and metabolic syndrome such as insulin resistance, hyperlipidemia, and obesity. Therefore, this study aimed to review the preclinical efficacy of A. orientale and its chemical constituents including Alisol A 24-acetate, Alisol B 23-acetate, Alisol F, and Alismol against NAFLD and metabolic syndrome. A. orientale prevented hepatic Triglyceride accumulation through suppressing de novo lipogenesis and increasing lipid export. In addition, it controlled oxidative stress markers, lipoapoptosis, liver injury panels, and inflammatory and fibrotic mediators, eventually influencing steatohepatitis and liver fibrosis.
Moreover, it exhibited pharmacological activities against hyperlipidemia, obesity, and hyperglycemia as well as appetite. These biological actions of A. orientale might contribute to adiponectin activation or a role as a farnesoid X receptor agonist. In particular, Alisol A 24-acetate and Alisol B 23-acetate could be expected as main compounds. Taken together, A. orientale might be an effective candidate agent for the treatment of NAFLD and its comorbidities, although further assessment of its standardization, safety test, and clinical trials is consistently required.
The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity.
Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.
Allicin
Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice
Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, Triglyceride, glucose, and hepatic cholesterol storage were determined.
Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24 ± 7.94% (P < 0.0001) with 5 mg/kg allicin, 39.28 ± 5.03% (P < 0.0001) with 10 mg/kg allicin, and 41.18 ± 5.00% (P < 0.0001) with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, Triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.
Allium cepavar. aggregatum G. Don extract
effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats
Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such asAtherosclerosis in the folk. This study was mainly aimed at investigating theeffects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of totalcholesterol (TC), Triglyceride (TG), low-density lipoproteincholesterol (LDL-C),high-density lipoproteincholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity inserum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyzeLDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis.
Furthermore, ACE reduced the levels of TC, TG,LDL-C, and MDA, and increased HDL levels and elevated SOD activity both inserum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and thelipid and foam cells of the aortic arch of the rats in ACE group were markedlyameliorated. WB results showed that ACE promoted the degradation of HMGCR and increasedLDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation ofLDLR. PRACTICAL APPLICATIONS:Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, duringAtherosclerosis development, hyperlipidemia is an important risk factor.
To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the sideeffects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such asAtherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation ofLDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statinlipid-lowering agent.
Studies on Antihyperliperlipemic and Antioxidant Activity of Allium cepa L.
This Study was attempted to investigate the effect of Allium cepa L. (onion) on the activities of GOT and GPT, the levels total lipids, Triglyceride , total cholesterol, phospholipid and ${\beta}-lipoprotein$ in the serum and the increase ratio of body and liver weight in the experimentally induced hyperlipemic rats. The activities of S-GOT and S-GPT were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the high lipid-diet control group. The levels of total lipids. Triglyceride , total cholesterol and phospholipids were significantly decreased in dose of onion juice 3 ml and 5 ml/head as compared to the control group, respectively. However, the level of ${\beta}-lipoprotein$ was significantly decreased in dose of onion juice 3 ml/head.
The levels of Triglyceride and total cholesterol in the liver were significanatly decreased in dose of onion juice 3 ml/head. Increase ratio of the body and liver weight were significantly decreased in dose of onion juice 3 ml/head. Anti-fatigue activity of onion juice were studied in mice using the swimming performance method. The potencies of anti-fatigue acti-vities was significantly found in 1.2 ml/head. p.o. of onion juice. The methanol extract and juice extract of onion was significantly found to have an antioxidative activity on the air oxidation of linoleic acid as compared to the 3-butyl-4-hydroxyanisole and ${\alpha}-tocopherol$.
Allium sativum extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
A 12-week intervention with KRG was conducted in patients with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed with T2DM. Subjects were randomized in a double-blind, placebo-controlled trial. The trial results showed that 12 weeks of intervention with KRG supplementation (5 g/day) led to normalization of whole blood and serum glucose levels as well as serum insulin and CRP concentrations (Bang et al., 2014). Administration of Panax Ginseng extract (PGE) for 8 weeks (6 g/day) decreased serum triglycerides and total cholesterol and LDL levels, while increasing HDL levels.
These results were attributed to PGE potent antioxidant effects (Kim and Park, 2003). In accordance, the effects of a low-dose (3 g/day) and a high-dose (6 g/day) of KRG supplementation for 8 weeks on antioxidant enzymes and oxidative stress markers in humans were assessed in a randomized, double-blind, placebo-controlled trial. Increased GSH-Px, SOD, and CAT activities were found in the high-dose group as compared to the placebo group. Plasma oxidized-LDL levels and DNA tail length and tail moment were significantly decreased in both high and low dose groups but increased in the placebo group. This led to the conclusion that supplementation with KRG upregulates antioxidant enzymes activities and consequently attenuates lymphocyte DNA damage (Lee et al., 2012).
cholesterollowering property of garlic (Allium sativum) on patients with hypercholesterolemia
Background: Cardiovascular disease especially atherosclerotic coronary heart disease (CHD) accounts for a large population of all deaths and disability worldwide. Elevatedlipid levels have a strong association with cardiovascular events. Objectives: Study aim is to reducecholesterol levels with garlic supplementation. Materials and Methods: It is a prospective, interventional open-label study to see theeffect of garlic onserumcholesterol levels. Study was conducted in the Department of Pharmacology and Therapeutics, Rajendra Institute of Medical Sciences, Ranchi. Fifty Healthy subjects with elevatedcholesterol levels between 240 and 330 mg/dL were enrolled. Subjects were given 3 g of raw garlic daily for a total period of 90 days.
Follow-up was done on 30th, 60th, and 90th day after starting treatment. Results: In male patients, theserumcholesterol level showed significant decrease of 13% (P < 0.001) from mean baseline of 269.30 mg/dL to 233.93 mg/dL at 90th day. In female patients, the decrease was 10% (P < 0.001) from mean baseline of 260.30 mg/dL to 233.90 mg/dL at 90th day. Conclusion: Garlic has a role incholesterol management as an adjunctive therapy in most cases of significant hypercholesterolemia therebyreducing risk ofAtherosclerosis and cardiovascular events.
A review on the effects of Allium sativum (Garlic) in metabolic syndrome
The metabolic syndrome is a common problem world-wide and includes abdominal obesity, hypertension, dyslipidemia, and hyperglycemia disorders. It leads to insulin resistance and the development of diabetes mellitus or cardiovascular disease. Allium sativum (garlic) has been documented to exhibit anti-diabetic, hypotensive, and hypolipidemic properties.
This suggests a potential role of A. sativum in the management of metabolic syndrome; however, more studies should be conducted to evaluate its effectiveness. In this review, we discussed the most relevant articles to find out the role of A. sativum in different components of metabolic syndrome and cardiovascular disease risk factors. Because human reports are rare, further studies are required to establish the clinical value of A. sativum in metabolic syndrome.
alpha-Linolenic acid
Alpha-linolenic acid (ALA) reduces cardiovascular disease (CVD) risk, possibly by favorably changing vascular inflammation and endothelial dysfunction. Inflammatory markers andlipids and lipoproteins were assessed in hypercholesterolemic subjects (n = 23) fed 2diets low in saturated fat andcholesterol, andhigh in PUFA varying in ALA (ALAdiet) and linoleic acid (LAdiet) compared with an average Americandiet (AAD). The ALAdiet provided 17% energy from PUFA (10.5% LA; 6.5% ALA); the LAdiet provided 16.4% energy from PUFA (12.6% LA; 3.6% ALA); and the AAD provided 8.7% energy from PUFA (7.7% LA; 0.8% ALA). The ALAdiet decreased C-reactive protein (CRP, P < 0.01), whereas the LAdiet tended to decrease CRP (P = 0.08).
Although the 2high-PUFAdiets similarly decreased intercellular cell adhesion molecule-1 vs. AAD (-19.1% by the ALAdiet, P < 0.01; -11.0% by the LAdiet, P < 0.01), the ALAdiet decreased vascular cell adhesion molecule-1 (VCAM-1, -15.6% vs. -3.1%, P < 0.01) and E-selectin (-14.6% vs. -8.1%, P < 0.01) more than the LAdiet. Changes in CRP and VCAM-1 were inversely associated with changes inserum eicosapentaenoic acid (EPA) (r = -0.496, P = 0.016; r = -0.418, P = 0.047), or EPA plus docosapentaenoic acid (r = -0.409, P = 0.053; r = -0.357, P = 0.091) after subjects consumed the ALAdiet. The 2high-PUFAdiets decreasedserum totalcholesterol,LDLcholesterol and Triglycerides similarly (P < 0.05); the ALAdiet decreased HDLcholesterol andapolipoprotein AI compared with the AAD (P < 0.05). ALA appears to decrease CVD risk by inhibiting vascular inflammation and endothelial activation beyond itslipid-lowering effects.
This meta-analysis aimed to investigate the impact of low-ratio linoleic acid/alpha-linolenic acid (LA/ALA) supplementation on the blood lipid profiles in adults. We conducted a systematic search for relevant randomized controlled trials (RCTs) assessing the effects of low-ratio LA/ALA using databases including PubMed, Embase, Cochrane, and Web of Science, as well as screened related references up until February 2023. The intervention effects were analyzed adopting weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis indicated that low-ratio LA/ALA supplementation decreased total cholesterol (TC, WMD: −0.09 mmol/L, 95% CI: −0.17, −0.01, p = 0.031, I2 = 33.2%), low-density lipoprotein cholesterol (LDL-C, WMD: −0.08 mmol/L, 95% CI: −0.13, −0.02, p = 0.007, I2 = 0.0%), and Triglycerides (TG, WMD: −0.05 mmol/L, 95% CI: −0.09, 0.00, p = 0.049, I2 = 0.0%) concentrations.
There was no significant effect on high-density lipoprotein cholesterol concentration (HDL-C, WMD: −0.00 mmol/L, 95% CI: −0.02, 0.02, p = 0.895, I2 = 0.0%). Subgroup analysis showed that low-ratio LA/ALA supplementation significantly decreased plasma TC, LDL-C, and TG concentrations when the intervention period was less than 12 weeks. In the subgroup analysis, a noteworthy decrease in both TC and LDL-C levels was observed in individuals receiving low-ratio LA/ALA supplementation in the range of 1–5. These findings suggest that this specific range could potentially be effective in reducing lipid profiles. The findings of this study provide additional evidence supporting the potential role of low-ratio LA/ALA supplementation in reducing TC, LDL-C, and TG concentrations, although no significant impact on HDL-C was observed.
Amaranthus viridis leaf extract
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due tohigh levels ofserumcholesterol.oxidizedLDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse healtheffects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components,hypocholesterolemic andAntiatheroscleroticeffects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits. Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, whilereverse Phase-high Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normaldiet, 2%highcholesteroldiet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively.
The supplementation with A. viridis extract significantly reduced totalcholesterol,LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries. Treatment with A. viridis extract also diminished the development of aortic plaques and decreased the intima : media ratio, as observed in simvastatin-treated rabbits. The phytocomponents of A. viridis have been reported to have therapeuticeffects in treating hypercholesterolemia andAtherosclerosis, and the in vivo study on A. viridis further confirms its potential as an alternative therapeutic agent.
Hypercholesterolemia is one of the main causes for coronary heart disease, which occurs due to high levels of serum cholesterol. Oxidized LDL accumulation leads to atherosclerotic plaque formation, which contributes to myocardial infarction and cardiovascular diseases. Consumption of statins leads to adverse health effects such as liver and muscle toxicity; thus attention is now focused on alternative treatments using chemicals of plant origin. This study is designed to investigate the phytochemical components, hypocholesterolemic and antiatherosclerotic effects of Amaranthus viridis (A. viridis) using hypercholesterolemic rabbits.
Gas Chromatography Mass Spectrometry (GC-MS/MS) analysis revealed 30 compounds, while Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) detected the presence of ascorbic acid, rutin, quercetin and catechin. An animal model study was performed on twenty New Zealand white rabbits that were randomly divided into 5 groups and fed with normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg kg−1 simvastatin, 2% HCD + 100 mg kg−1 A. viridis extract and 2% HCD + 200 mg kg−1 A. viridis extract, respectively. The supplementation with A. viridis extract significantly reduced total cholesterol, LDL and Triglyceride levels, and increased the levels of HDL and antioxidant enzymes (SOD and GPx). The elevated levels of AST, ALT and creatine kinase indicate liver and muscle injuries.
To investigate the antihyperglycemic and hypolipidemic effects of methanolic extract of leaves of Amaranthus viridis (MEAV) in normal and Streptozotocin (STZ) induced diabetic rats. The anti-hyperglycemic and hypolipidemic activity of methanolic extract of leaves of Amaranthus viridis was evaluated by using normal and STZ induced diabetic rats at dose of 200 mg/kg and 400 mg/kg by mouth per day for 21 days. Blood glucose levels and body weight was monitored at specific intervals, and different biochemical parameters, serum cholesterol, serum Triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein were also assessed in the experimental animals. Histology of pancreas was performed.
The statistical data indicated a significant increase in the body weight, decrease in the blood glucose, total cholesterol and serum Triglycerides after treatment with MEAV. High density lipoprotein (HDL) cholesterol level was significantly increased when treated with extract. Histologically, focal necrosis was observed in the diabetic rat pancreas; however, was less obvious in treated groups. The MEAV has beneficial effects in reducing the elevated blood glucose level and body weight changes, and improves the lipid profile of STZ induced rats.
Amomum subulatum seeds (Family Zingiberaceae)
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated incholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenicdiet for 120 days resulted in a significant increase inserum totalcholesterol, phospholipid and Triglyceride levels when compared with control group. The levels ofLDL and VLDL-cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase inlipid peroxidation and reduction in glutathione (GSH) and catalase activity.
The level oflipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in totalcholesterol, Triglyceride , phospholipid,LDL and VLDLcholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesseslipid-lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
In the present study, hypolipidemic activity of fraction (50:50; CHCl3:CH3OH) of Amomum subulatum (Zingiberaceae) seeds was evaluated in cholesterol-fed rabbits. Hyperlipidemia induced by feeding atherogenic diet for 120 days resulted in a significant increase in serum total cholesterol, phospholipid and Triglyceride levels when compared with control group. The levels of LDL and VLDL-cholesterol were increased significantly, but the HDL-cholesterol ratio was decreased. The changes in the antioxidant parameters were accompanied by an increase in lipid peroxidation and reduction in glutathione (GSH) and catalase activity.
The level of lipid peroxidation was reduced whereas GSH content and catalase activity were elevated after the treatment with A. subulatum fraction at the dose level of 100 mg/kg.b.wt/day. A significant reduction was observed in total cholesterol, Triglyceride , phospholipid, LDL and VLDL cholesterol where as HDL-cholesterol ratio was increased after administration of A. subulatum. The results of the present study indicate that fraction of A. subulatum possesses lipid-lowering and antioxidant activity and could be beneficial in the treatment of hyperlipidemia.
Ananas comosus
Background: Pineapple peel is a waste component of pineapple with valuable source of metabolites as phytoactive compounds in ameliorating metabolic-related disorders. This study investigated the atheroprotective and neuroprotectiveeffects of peel extract of Ananas comosus fruit (PEAC) in normaldiet (ND) andhigh-fatdiet (HFD) fed rats.
Methods: Male Wistar rats were fed ND or HFD for 9 weeks, and beginning from the 6th week animals were also orally treated with PEAC (200 mg/kg). Memory performance was assessed using Y-maze test (YMT) and novel object recognition test (NORT) while anxiolytic-likeeffect was assessed on the elevated plus maze (EPM).serumcholesterol, Triglycerides and HDL-C were determined, whileLDL-C and atherogenic risk calculated.serum and brain tissue malondialdehyde, reduced glutathione, catalase were determined. Brain acetylcholinesterase activity and interleukin-6 level were also determined.
Results: PEAC significantly attenuated HFD-induced reduction in correct alternation in YMT, and discrimination index in NORT. Also, PEAC demonstrated anxiolytic-like activity in EPM test. PEAC significantlyimprovedlipid profile and decreased risk of atherogenicity in ND and HFD-fed rats. In addition, PEAC improvesserum and brain antioxidant status by decreasing malondialdehyde and increasing GSH and catalase. PEAC significantly impaired HFD-induced brain acetylcholinesterase activity and IL-6 levels.
Conclusion: These findings suggest that peel extract of Ananas comosus fruit may protect againstdiet-induced behavioral disturbances via atheroprotective, antioxidants and anti-inflammatory activities.
In this study, we investigated hypolipidemic mechanisms of the ethanolic extract of Ananas comosus L. leaves (AC) in mice and then determined its activities in related enzymes. The results showed that AC (0.40 g/kg) significantly inhibited the increase in serum Triglycerides by 40% in fructose-fed mice. In mice induced by alloxan and high-fat diets, serum total cholesterol remained at a high level (180 – 220 mg/dl) within 7 days of removing high-fat diets but reached normal level (120 – 140 mg/dl) after AC (0.40 g/kg per day) treatment. Also, AC (0.40 and 0.80 g/kg) significantly inhibited serum lipids from the increase in Triton WR-1339-induced hyperlipidemic mice. AC (0.01 – 100 µg/ml) selectively activated lipoprotein lipase (LPL) activity by 200% – 400% and significantly inhibited 3-hydroxyl-methyl glutaryl coenzyme A (HMGCoA) reductase activity by 20% – 49% in vitro.
Furthermore, 2 months of fenofibrate (0.20 g/kg) administration particularly increased mice liver weights (0.0760 ± 0.0110 g/g) while AC (0.40 g/kg) had no effect (0.0403 ± 0.0047). Taken together, these results suggest that AC will be a new potential natural product for the treatment of hyperlipidemia that exerts its actions through mechanisms of inhibiting HMGCoA reductase and activating LPL activities. Its action mechanisms differentiate from those with fibrates but may be partly similar to those with statins. It is hopeful that AC may serve as the adjuvant for fibrates.
andrographolide
Triglyceride Andrographolide, a natural anti-inflammatory agent: An Update
Andrographolide can reduce liver Triglyceride content and liver macrophage infiltration and reduce the expression of proinflammatory and profibrotic genes in the liver in mice with nonalcoholic steatohepatitis. It can also inhibit NF-κB activity and the activity of the NLRP3 inflammasome in high-fat HepG2 cells to reduce liver inflammation and fibrosis (Cabrera et al., 2017).
A study has shown that in hepatic stellate cells, andrographolide can effectively reduce liver inflammation and fibrosis by suppressing the activity of the TLR4/NF-κB and TGF-β1/Smad2 signalling pathways (Lin et al., 2018). 14-Deoxy-11,12-didehydroandrographolide partially ameliorated steatohepatitis, liver fibrosis and liver injury in high-fat, high-cholesterol diet-induced fatty liver disease by enhancing hepatic Nrf2-mediated downstream antioxidant enzyme activity and inhibiting NLRP3 inflammasome activation, which can down-regulate the expression of NLRP3, Caspase-1 and IL-1β, and this anti-inflammatory property may be achieved by inhibiting the NF-κB signaling pathway.
Angelica sinensis (Oliv.) Diels.extract
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potentialAnti-atheroscleroticeffects by preventingoxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protectiveeffects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined byhigh performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. Theeffect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play anAnti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
In the present work, ASP with low MW was isolated via an optimized “one-step” purification process. The well-known traditional water extraction and alcohol precipitation methodology were adopted to acquire crude polysaccharides. Then, the crude extraction was purified by D315 weak-base ion-exchange resin which is believed to play an effective role in purification and absorption (Fan et al., 2018). After lyophilization, ASP (MW = 3.2 kDa) was obtained and subjected to free fatty acid (FFAs)-induced L02 cell lines in vitro.
It was speculated that ASP could decrease the level of triglyceride (TG) and total cholesterol (TC) level in supernatant. Also, through Oil Red O (ORO) and Nile red staining, ASP was postulated to ameliorate lipid accumulation in FFAs-induced cells. In order to investigate the lipid-lowering function of ASP in vivo, NAFLD model was established by feeding the ICR male mice (3–4 weeks) with HFD.
Annurca Apple Polyphenols
Background: Angelica root is the dry root of the Umbelliferae plant Angelica sinensis (oliv) Diels. Angelica organic acid (OA) is the main active ingredient in Angelica sinensis, and it exerts potentialAnti-atheroscleroticeffects by preventingoxidized low-density lipoprotein (Ox-LDL) induced endothelial injury. To study the protectiveeffects of OA on ox-LDL-induced HUVECs autophagic flux dysfunction and inflammatory injury.
Methods: OA were isolated by water extraction and alcohol precipitation, and then the content of ferulic acid (FA) in the OA was determined byhigh performance liquid chromatography. The ox-LDL-induced endothelial injury model was established. Theeffect of ferulic acid on the survival of Human umbilical vein endothelial cells (HVUECs) was detected by CCK-8 assay. HUVECs were pretreated with different concentrations of OA (20 μmol/L, 40 μmol/L, and 80 μmol/L), and Western Blot was used to detect the expressions of LC3II, p62, MCP-1, VCAM-1 and LOX-1. The autophagosomes in HUVECs were observed by transmission electron microscopy (TEM).
Results: 20 μmol/L OA could increase the expression of LC3II and decrease the expression of p62, MCP-1, VCAM-1 and LOX-1. The results of TEM showed that angelica organic acids promoted cell organelle degradation in autolysosomes.
Conclusion: OA could reduce inflammation, protect endothelial cells and play anAnti-atherosclerotic role by enhancing the autophagy flux of damaged endothelial cells, in which FA the major active ingredient of OA played a major role.
Aim: Cardiovascular disease (CVD) are among the main causes of death worldwide and dyslipidemias account for one of the risk factors for these diseases. Habitual apple consumption appears to be inversely associated with reduced cardiovascular risk. Then, this systematic review aims to investigate the effect of chronic apple consumption on the lipid profile of adults with dyslipidemia.
Methods: A systematic search was performed in electronic databases, including PubMed, Embase, Web of Science and Scopus, without restriction of year of publication. Inclusion criteria were randomized clinical trials in humans that investigated the effect of chronic consumption of whole fresh or dried apple, for a period longer than two weeks of intervention on the lipid profile.
Results: Based on the methodology used and following the pre-established search strategies, 4,468 articles were found. After applying the inclusion and exclusion criteria, five articles were selected for qualitative evaluation, covering 522 adult participants of both sexes. Three randomized controlled trials included in this review demonstrated that there was a decrease in plasma total cholesterol (TC), Triglyceride and low-density lipoprotein cholesterol (LDL-c) concentrations, in addition to an increase in high-density lipoprotein cholesterol (HDL-c) concentration. Two other studies found different results. Low risk of bias was identified in three studies.
Conclusions: The analysis of the studies indicates that the consumption of fresh and/or dried apples with the peel has a beneficial effect on the lipid profile of adults, with a decrease in TC and LDL-c. These effects may be related to polyphenols and soluble fibers, among other functional compounds present in this fruit.
Antrodia Camphorata
TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent-Metf (36.5%). TT-treated mice reduced the HFD-induced hyperglycemia, hyper Triglyceride mia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE-treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase), an inhibitor of hepatic glucose production.
The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK) phosphorylation in mice. TT-treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and increased mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a). These mice also exhibited decreased expression levels of lipogenic fatty acid synthase (FAS) in liver and adipose tissue and reduced mRNA levels of hepatic adipocyte fatty acid binding protein 2 (aP2) and glycerol-3-phosphate acyltransferase (GPAT). These alterations resulted in a reduction in fat stores within the liver and lower Triglyceride levels in blood.
Our results demonstrate that TT is an excellent therapeutic approach for the treatment of type 2 diabetes and hyper Triglyceride mia.
The aim of this study was to examine the effects of dehydroeburicoic acid (TT) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were randomly divided into six groups and given orally by gavage TT (at three dosages), metformin (Metf), fenfibrate (Feno), or vehicle for 4 weeks. STZ-induced diabetic mice showed elevations in blood glucose levels (P < 0.001). TT treatment markedly decreased blood glucose levels by 42.6–46.5%. Moreover, STZ-induced diabetic mice displayed an increase in circulating Triglyceride (TG) and total cholesterol (TC) levels (P < 0.001 and P < 0.01, respectively) but a decrease in blood insulin and adiponectin levels (P < 0.01 and P < 0.05, respectively). These substances are also reversed by TT treatment, indicating TT ameliorated diabetes and dyslipidemia.
Membrane skeletal muscular expression levels of glucose transporter 4 (GLUT4) and expression levels of AMPK phosphorylation (phospho-AMPK) in both liver and skeletal muscle were reduced in STZ-induced diabetic mice, which normalized upon TT treatment and correction of hyperglycemia accompanied with a decrease in mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6 Pase), which was related to the inhibition of hepatic glucose production and attenuating diabetic state. In addition, TT also showed hypolipidemic effect by increasing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a) but decreasing expression levels of fatty acid synthase (FAS), which further contributed to a decrease in circulating TG levels. TT-treated mice displayed decreased SREBP2 mRNA levels and reduced blood TC levels. These findings strongly support that TT prevents diabetic and dyslipidemic states in STZ-induced diabetic mice evidenced by regulation of GLUT4, PPARα, FAS, and phosphorylation of AMPK.
The present study was designed to evaluate the protective effect of sulphurenic acid (SA), a pure compound from Antrodia camphorata, on diabetes and hyperlipidemia in an animal model study and to clarify the underlying molecular mechanism. Diabetes was induced by daily 55 mg/kg intraperitoneal injections of streptozotocin (STZ) solution over five days. Diabetic mice were randomly divided into six groups and orally gavaged with SA (at three dosages) or glibenclamide (Glib), fenofibrate (Feno) or vehicle for 3 weeks. Our findings showed that STZ-induced diabetic mice had significantly increased fasting blood glucose, glycated hemoglobin (HbA1C), plasma Triglyceride (TG), and total cholesterol (TC) levels (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) but decreased blood insulin, adiponectin, and leptin levels compared to those of the control group (p < 0.001, p < 0.001, and p < 0.001, respectively).
Administration of SA to STZ-induced diabetic mice may lower blood glucose but it increased the insulin levels with restoration of the size of the islets of Langerhans cells, implying that SA protected against STZ-induced diabetic states within the pancreas. At the molecular level, SA treatment exerts an increase in skeletal muscle expression levels of membrane glucose transporter 4 (GLUT4) and phospho-Akt to increase the membrane glucose uptake, but the mRNA levels of PEPCK and G6Pase are decreased to inhibit hepatic glucose production, thus leading to its hypoglycemic effect. Moreover, SA may cause hypolipidemic effects not only by enhancing hepatic expression levels of peroxisome proliferator-activated receptor α (PPARα) with increased fatty acid oxidation but also by reducing lipogenic fatty acid synthase (FAS) as well as reducing mRNA levels of sterol regulatory element binding protein (SREBP)1C and SREBP2 to lower blood TG and TC levels. Our findings demonstrated that SA displayed a protective effect against type 1 diabetes and a hyperlipidemic state in STZ-induced diabetic mice.
Antrodia cinnamomea
Antrodia cinnamomea is a Taiwanese medicinal mushroom with multiple pharmacological activities. Antrodia cinnamomea solid-state cultivated mycelium (LAC) exerts health-relatedeffects in animal and cell models, but clinical data is limited. This study aimed to determine the safety andeffects of LAC on human physiological functions. In an open-label, single-arm study, 32 healthy men and women ingested LAC capsules for three months. The subjects were monitored during the study and one month after the study end-point. LAC consumption did not significantly change fastingbloodglucose,blood pressure, and Triglyceride levels or liver and renal function indices. No adverse events occurred during the trial. Moreover, a significant change from baseline in totalcholesterol levels was observed; men and women had decreases of 5.7% and 5.3%, respectively. Based on these, the ingestion of LAC-capsule has a considerable degree of safety and has the potential to reduce total cholesterol in healthy adults.
Evaluation of Blood Lipid-Lowering Effects of Antrodia cinnamomea Mycelia Powder Complex
Objective: This study was conducted to assess the prenatal developmental blood lipid-lowering effects of an Antrodia cinnamomea mycelia powder complex according to the safety assessment guideline of Health Food announced by Ministry of Health and welfare, Executive Yuan of Taiwan. Methods: A total of 32 hyperlipidemia individuals with TC > 200 mg/dl were randomly divided in- to intervention group (n = 16) and placebo group (n = 16). Dietary intervention was provided for the intervention group for 2 months. Information on dietary intakes, physical examinations and blood samples was collected. Serum lipids were assayed at baseline and endpoint of the study pe- riod. Subjects take two capsules of A. cinnamomea mycelia powder complex or placebo twice a day. The study has 2 weeks run in period, 8 weeks intervention period, and 4 weeks follow-up period.
All subjects measure body weight, body fat, blood pressure and biochemical parameters, including Triglycerides (TG), total cholesterol (TC), low density lipoprotein in cholesterol (LDL-C), high den- sity lipoprotein in cholesterol (HDL-C), blood sugar, kidney and liver function. Results: The results were found after 8 weeks intervention, the plasma total cholesterol and LDL-C were significantly decreased compared with the initial, and there was significantly difference (p < 0.05) compared with the placebo group. LDL-C/HDL-C and Triglyceride level has a decreasing trend. Conclusion: A. cinnamomea mycelia powder complex could decrease blood lipids.
The major pathologic hallmark of the alcoholic liver disease (ALD) is the representation of chronic alcohol-induced hepatocyte lipid accumulation. This study aims to investigate the hepatoprotective role of triterpenoids-enriched extracts from Antrodia cinnamomea mycelia (ACT) in chronic alcohol-induced liver injury mice, establishing in C57BL/6 mice through gradient alcohol feeding for 24 weeks. In long-term alcohol consumption mice, the significantly lost body weight, increased organ indexes, hepatic alanine aminotransferase and aspartate aminotransferase levels were all remissed after 6-week ACT orally administration, showing its hepatoprotective property. ACT suppressed the Triglyceride , total cholesterol and low-density lipoprotein levels, and enhanced high-density lipoprotein levels in serum or/and liver of chronic alcohol damaged mice.
Combining with the pathological observations, ACT displayed an anti-steatosis effects to restrain the progress of ALD. Based on proteomic analysis and enzyme-linked immunosorbent assay, ACT had been confirmed to regulate the levels of lipid biogeneration-related factors and depressed the over-accumulation of hepatic reactive oxygen species. According to further data, ACT prevented alcoholic liver injury may be associated with mediating lipid metabolism-related to PGC-1α and NF-κB signaling. In summary, ACT protected the body against chronic alcohol ingest induced liver injury through its regulation lipid on metabolism.
HYPOLIPIDEMIC EFFECTS OF ANTRODIA CINNAMOMEA EXTRACTS IN HIGH-FAT DIET-FED HAMSTERS
Antrodia cinnamomea (AC) is a popular medicinal fungus used for treating hypertension, hepatotoxicity and tumors. This study aimed to examine the hypolipidemic properties of A. cinnamomea extracts (ACE) in high-fat diet-fed hamsters. Results showed that at concentrations 500, 1,000 and 1,500 mg/kg, ACE showed no significant effect on total cholesterol and high-density lipoprotein concentrations, but a trend of decrease in plasma Triglycerides and low-density lipoprotein (LDL) levels was noted, and a significant reduction in LDL was observed at 1,500mg/kg ACE. ACE caused a significant decrease in liver Triglycerides and total cholesterol concentrations. ACE possessed the ability to enhance superoxide dismutase, catalase and glutathione peroxidase production, and reduced the thiobarbituric acid-reactive substances level in hyperlipidemic hamsters. These results conclude that ACE is able to lower the plasma Triglycerides and LDL, liver Triglycerides and total cholesterol concentrations, as well as enhancing the level of antioxidant enzymes.
apigenin 7-O-β-D glucoside
Oral administration of apigenin 7-O-β-D glucosidereverses hyperlipidemia and associated
vascular dysfunction in rats
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti-inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate theeffect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01),
totalcholesterol,LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemiceffect. Thiseffect wasfurther confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis ofcholesterol.
Apigenin 7‑O‑β‑D‑glucoside is a flavonoid reported as smooth muscle relaxant, anti- inflammatory, and anti-oxidant, suggesting its role in cardiovascular disease. The present study aimed to investigate the effect of apigenin 7‑O‑β‑D‑glucoside on hyperlipidemia and associated vascular dysfunction in rats. Oral administration of apigenin 7‑O‑β‑D‑glucoside to HFD and tyloxopol-induced hyperlipidemic SD rats for 28 and 10 days that reduced significantly (p < 0.01), total cholesterol, LDL, VLDL and Triglycerides , and increased HDL levels and also reduced the total body weight and atherogenic index suggesting its antihyperlipidemic effect.
This effect was further confirmed when the compound also inhibited the key enzyme HMG-CoA reductase in the biosynthesis of cholesterol. The devastating effects on vascular architecture such as change in the aortic intima, media, adventitia and also the endothelium damage, were reversed in apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day treated group. In the in vitro studies, the compound reversed the endothelial damage demonstrated by significant vasorelaxation in the aortic rings from hyperlipidemic rats treated with apigenin 7‑O‑β‑D‑glucoside 5 mg/kg/day, with EC50 value of 0.02 μg/mL (0.01-0.20) compared to hyperlipidemic HFD rats, similar to atorvastatin. These findings indicate that antihyperlipidemic effect of apigenin 7‑O‑β‑D‑glucoside is mediated through decrease in total cholesterol, LDL, VLDL, Triglyceride level and increase in level of HDL through inhibition of HMG-CoA inhibition and also improved the associated histopathological changes and endothelium dysfunction.
Apocynum venetum
Apocynum leaf extract inhibits the progress of atherosclerosis in rats via the AMPK/mTOR pathway
Apocynum leaf extract is an extract of the dried leaves of Apocynum venetum (a member of the Apocynaceae family) that has many effects on the cardiovascular system. The aim of the present study was to evaluate the protective effects of apocynum leaf extract on the atherosclerosis in rats induced by high-fat diet combined with vitamin D3 intraperitoneal injection. The atherosclerosis in rats were induced with a high-fat diet and an intraperitoneal injection of VD3 once daily for three contiguous days at a total injection dose of 70 U/kg. At the end of the 18th week, serum total cholesterol (TC) and Triglyceride (TG) contents were measured. Hydroxyproline content in the aorta were measured by the alkali hydrolysis method. The hematoxylin-eosin (HE) and immunohistochemical staining were applied to evaluate the morphological changes and the collagen I and α-smooth muscle actin expression. The protein expression and the mRNA level of AMPK and mTOR were detected by western blot analysis and reverse transcript PCR.
Areca catechu L. Extract
Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on Triglyceride absorption in Triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of Triglyceride and the plasma lipid concentration. The absorbed Triglyceride that appeared in the blood after an oral dose of [9,10(n)-3H] Triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group.
Aporosa lindleyana
cholesterolloweringeffect OF Aporosa lindleyana IN MALE WISTAR RATS
Aporosa lindleyana is a green leafy vegetable of family Euphorbiaceae grown in tropical countries. In this study theeffect of Aporosa lindleyana on theserumcholesterol level of hypercholestero-laemic rats and normocholesterolaemic Wistar rats fed on acholesterol enricheddiet was investigated. The results indicate that feeding of plant extract for two weeks reduces the total cholesterol in hypercholesterolaemic Wistar rats by 25.2% and normocholesterolaemic rats fed with cholesterol enricheddiet by 37.7%. In addition the test group had significantly lower (p<0.05) total/HDL than the controls indicating that Aporosa lindleyana extract possesses hypochlosterolaemic activity.
Artemisia capillaris Thunb.extract
Antioxidant andlipid-lowering effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Objectives: This study was designed to evaluatelipid-lowering and antioxidanteffects of Artemisia capillaris (A. capillaris) using a model of hyperlipidemic rats induced by poloxamer-407.
Methods: Rats were previously treated by A. capillaris water extract, and intraperitoneally injected by poloxamer-407 to induce hyperlipidemia. Parameters of serum lipid and oxidative stress biomarkers were determined.
Results:
1. A. capillarisameliorated the elevation ofserum totalcholesterol, Triglyceride, LDL-cholesterol and MDA level.
2. A. capillarisameliorated the reduction ofserum TAC and SOD activities.
3. A. capillarisameliorated the reduction ofserum GSH and GSH-reductase level.
Conclusions: According to these results, A. capillaris can be used to treat hyperlipidemia or as basis for making new drugs for treating hyperlipidemia in the future.
Antioxidant and Lipid-lowering Effects of Artemisia capillaris on a Rat Model of Hyperlipidemia
Hyperlipidemia, also known as hyperlipoproteinemia, refers to the excess status of fatty substances including cholesterol, Triglycerides or lipoproteins in the bloodstream1,2). Hyperlipidemia is an important risk factor in developing heart disease and stroke which are leading causes of death in most developed countries, including Korea3,4). Accordingly, the appropriate control of lipid levels in the bloodstream is a standard strategy to prevent the development of vascular disease5). There are four classes of lipid lowering drugs: 3-hydroxy-3-methylglutaryl coenzyme A(HMG- CoA) reductase inhibitors commonly referred to as statins, bile acid sequestrants, nicotinic acid, and fibric acids6,7). These hypolipidemic agents lower lipid levels somewhat, but have a limitation due to lack of final clinical outcome in prevention of heart disease and stroke, and often adverse effects such as hepatotoxicity, myopathy or noncardiovascular death8,9)
Artemisinin (Artemisia annua L.)
Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes.
Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and Triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively.
Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release.
Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.
Artemisia annua extract ameliorates high-fat diet-induced fatty liver by activating AMPK
Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Recently, natural compounds that may be beneficial for improving NAFLD have received increasing attention. Artemisia annua L. is the source of antimalarial phytomolecule, artemisinin, which has been reported to prevent obesity. However, the effect of A. annua extract on hepatic lipid metabolism remains unclear. This study was performed to determine the protective effect of Artemisia annua extract (AAE) on high-fat diet (HFD)-induced hepatic lipid accumulation, and elucidate the molecular mechanisms behind its effects in vivo and in vitro. We found that HFD-fed mice with AAE administration (50 mg/kg/day) for 8 weeks dramatically reduced hepatic lipid accumulation compared to the control mice taken with HFD alone.
The body and liver weights of AAE group were significantly lower than those of HFD group, and oral administration of AAE remarkably suppressed the serum levels of Triglyceride (TG), total cholesterol (TC), fasting glucose, alanine transaminase (ALT) and aspartate transaminase (AST) in HFD-fed mice. AAE significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of HFD-fed mice and HepG2 hepatocytes. Moreover, AAE downregulated the hepatic expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in HFD-fed mice and high glucose-treated HepG2 cells. In addition, the inhibitory effects of AAE on the overexpression of SREBP-1c and FAS were attenuated by compound C, which is the specific AMPK inhibitor, in high glucose-treated HepG2 cells. These results indicated that AAE may represent a promising approach for the prevention and treatment of obesity-related NAFLD via the activation of AMPK and the regulation of AMPK-dependent lipogenic genes.
Artichoke Extract cynarin
General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or Triglyceride levels.
Artocarpus ovatus Blanco
Artocarpus ovatus Blanco is a plant species of the Philippines belonging to the family Moraceae. This study evaluated thecholesterol-lowering activity of the A. ovatus ethanolic leaf extract in Sprague Dawley rats and its acute oral toxicity. It was found to be safe and non-toxic up to 2000 mg/kg BW of test animals based on the guidelines of OECD 425 main test. Post toxicity test gross necropsy results are unremarkable. In thecholesterollowering bioassay, the ethanolic extract treated rats at doses of 200, 400 and 600 mg/kg showed time dependent reduction ofserum levels of totalcholesterol, Triglycerides and low density lipoproteins with p-values less than 0.05.high density lipoproteins concentrationimproved,high catalase enzyme levels and unremarkable degree oflipid peroxidation were measured and observed after 14 days of oral administration of the extract.
In vivo cholesterol-lowering bioassay results Mean serum total cholesterol, Triglycerides , HDL and LDL values were significant to all the experimental groups (p values < 0.05). After the 14-day treatment period, groups III, IV, V and VI (200 to 600 mg/kg extract treated groups and positive control group) have decreased total cholesterol, Triglycerides and LDL levels. However post hoc analysis showed that groups IV and V (400 and 600 mg/kg extract treated groups) have no significant difference in reducing total cholesterol. The treatment groups (200 to 600 mg/kg extract treated groups) do not statistically differ in improving mean HDL serum levels with the positive control group (p values > 0.05). This demonstrates that the ethanolic extract exhibited cholesterol-lowering effect comparable to the positive control on animal rat models.
Presence of excessive levels of cholesterol in the blood indicates a strong risk factor for cardiovascular diseases. Maintenance of low levels of cholesterol in the blood is clinically and importantly considered through the use of pharmaceutical agents such as the statin drugs (HMG-CoA reductase inhibitors) and the fibrates [11]. Medicinal plants can also be utilized as alternative sources of these established remedies but most of them must be clinically studied further. The results of this study suggest that the A. ovatus ethanolic leaf extract have a medicinal potential specifically in lowering cholesterol levels in rat animal models. Figures 1 to 4 present the mean total cholesterol, Triglycerides , HDL and LDL levels of the experimental groups.
Astragalus membranaceus
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protectiveeffects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments anddiet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of totalcholesterol andLDLcholesterol (P < 0.05 to 0.01), increased HDLcholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and thiseffect increased withhigher TFA concentration. In in vivo experiments, TFAeffectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve theAtherosclerosis profile.
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol ( to 0.01), increased HDL cholesterol levels ( ), and reduced the aortic fatty streak area by 43.6 to 63.6% ( ). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile.
Astragalus membranaceus is a Traditional Chinese Medicine (TCM) belonging to the Leguminosae family. It has been used as antidiabetic, cardioprotective, and hepatoprotective in the TCM clinic. From the stems of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, 14 oleanane type saponins (1–14) including eight new ones, astroolesaponins A (1), B (2), C1 (3), C2 (4), D (5), E1 (6), E2 (7), and F (8) were obtained, and their structures were elucidated by chemical and spectroscopic methods. Compounds 1–5, 7, 8, 11, and 13 showed decreased effects on Triglyceride levels in sodium oleate induced HepG2 cells.
Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer’s disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic Triglyceride . Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.
Astragalus mongholicus
Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protectiveeffects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments anddiet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of totalcholesterol andLDLcholesterol (P < 0.05 to 0.01), increased HDLcholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and thiseffect increased withhigher TFA concentration. In in vivo experiments, TFAeffectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve theAtherosclerosis profile.
Astragalus mongholicus is a Chinese traditional medicine. In this study, we sought to explore potential benefits in cardiovascular disorders associated with excess cholesterol and hyperlipidemia. We have investigated the effects of A. mongholicus extract as a dietary supplement on hyperlipidemia and oxidative stress in rats maintained on a high- cholesterol diet. Diets were supplemented with A. mongholicus extract at 0.4 and 0.8% for five weeks, while control animals received no supplement. A. mongholicus extract administration to hyperlipidemic rats resulted in a significant decline in serum levels of total cholesterol, Triglycerides and low density lipoprotein-cholesterol, with an increase in serum high-density lipoprotein-cholesterol levels. Furthermore, A. mongholicus extract improved serum and heart antioxidant status as assessed by superoxide dismutase and glutathione peroxidase activities and reduced levels of lipid peroxidation. These results suggest that A. mongholicus extract consumption can improve lipid profiles, inhibit peroxidation, and increase the activity of antioxidant enzymes, and is thereby likely to reduce the risk of coronary heart disease associated with hyperlipidemia and oxidative stress.
Avena sativa extract β- glucan
There was a significant reduction in blood glucose, serum liver enzymes, Triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups.
Basella alba
Hypercholesterolemia is the major risk factor that leads toAtherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse healtheffects, especially liver and muscle toxicity. This study was designed to investigate thehypocholesterolemic andAntiatheroscleroticeffects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varyingdiets: normaldiet, 2%highcholesteroldiet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of totalcholesterol,LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia andAtherosclerosis.
Twenty New Zealand white rabbits were divided into 5 groups and fed with normal diet (G1), 2% high cholesterol diet (HCD) (G2), 2% HCD + 10 mg/kg simvastatin
(G3), 2% HCD + 100 mg/kg B. alba extract (G4) and 2% HCD + 200 mg/kg B. alba extract (G5), respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol (TC), low density lipoptotein (LDL) and Triglyceride (TG). The significant increase in high density lipoprotein (HDL) and antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels observed in treatment with B. alba extract (G4 and G5) compared to the treatment with simvastatin (G3). The elevated levels of liver enzymes; alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and muscle enzyme; creatine kinase (CK) were noted in G2 and G3 indicate liver and muscle injuries. Treatment with simvastatin (G3) and B. alba extract (G4 and G5) significantly suppressed the aortic plaque formation. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
The enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway that produces cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed. In this study, 25 medicinal plant methanol extracts were screened for anti-HMG-CoA reductase activity. Basella alba leaf extract showed the highest inhibitory effect at about 74%. Thus, B. alba was examined in order to investigate its phytochemical components. Gas chromatography with tandem mass spectrometry and reversed phase high-performance liquid chromatography analysis revealed the presence of phenol 2,6-bis(1,1-dimethylethyl), 1-heptatriacotanol, oleic acid, eicosyl ester, naringin, apigenin, luteolin, ascorbic acid, and α-tocopherol, which have been reported to possess antihypercholesterolemic effects. Further investigation of in vivo models should be performed in order to confirm its potential as an alternative treatment for hypercholesterolemia and related cardiovascular diseases.
Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and Triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
Berberine
Regulation ofPCSK9 by nutraceuticals
PCSK9, a criticalInhibitor ofLDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulatesLDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepaticLDLR via inhibiting HNF1α which is a specific transcription factor
forPCSK9 gene. Statins increase the expression of bothPCSK9 andLDLR through the activation of SREBP-2,
resulting inPCSK9-mediated attenuation of theireffects.
Naturally OccurringPCSK9Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
The aim of this study was to investigate the role of the mevalonate pathway in the cytostatic/cytotoxiceffects of berberine, a natural plant alkaloid that reducescholesterol concentration. Berberine as well as lovastatin, anInhibitor of the mevalonate pathway, exerted dose-dependent cytostatic/cytotoxiceffects against human breast cancer cells (MDA-MB231). Although the mevalonate pathway metabolites (mevalonic acid, farnesyl pyrophosphate, geranylgeranyl pyrophosphate)effectivelyreversed cytostatic/cytotoxiceffects of lovastatin against MDA-MB231 cells, they were noteffective in influencing the cytostatic/cytotoxiceffects of berberine. The cytostatic/cytotoxiceffects of berberine do not seem to result from inhibition of the mevalonate pathway.
Ethnopharmacological relevance
Rhizoma coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumors. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of R. coptidis that contribute to the pharmacological efficacy of the herb.
Aim of the study
Pharmacokinetic studies have indicated that BBR has poor oral bioavailability. Interestingly, several reports show that absorbed BBR is extensively metabolized in rats and humans. We speculate that the BBR metabolites might be responsible for the pharmacological effects. The aim of this study is to examine BBR metabolites for their Triglyceride (TG)-lowering activities and the molecular mechanism to clarify BBR genuine effective forms in vivo.
Materials and methods
Four BBR metabolites were examined their TG-lowering effects with a commercial Triglyceride assay kit. Real-time PCR and Western blotting were used to confirm genes and proteins of interest, respectively.
Results
Among those BBR metabolites, M2 exhibited the more potential effects on TG-lowering and AMP-activated protein kinase (AMPK) activation in Hep G2 cells as compared with BBR. Moreover, BBR and M2 inhibited gene expressions of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), but motivated gene expression of medium chain acyl-CoA dehydrogenase (mCAD) significantly.
Conclusions
The results suggested that the TG-lowering effects of BBR and M2 might be partially mediated by the up-regulation of lipolysis gene expressions and down-regulation of lipogenesis gene expressions through activation of the AMPK signaling pathway. BBR and its metabolites might be in vivo active forms of oral doses of BBR, and M2 might be a promising drug candidate against hyperlipidemia.
Lipid-lowering effect of berberine in human subjects and rats
Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of Triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of Triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p = 0.11). Blood inflammatory factors (CRP, IL-6, TNFα, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.
Effects of berberine on lipid profile in subjects with low cardiovascular risk
Objective: To evaluate the efficacy as antihypercholesterolemic agent of berberine in patients with low cardiovascular risk.
Research design and methods: 144 Caucasian subjects were enrolled. After a 6-month run-in period following diet and practicing physical activity, patients were randomized to take placebo or berberine 500 mg twice a day, for 3 months, in a double-blind, placebo-controlled design. Berberine and placebo were then interrupted for 2 months (washout period), and all patients continued with only diet and physical activity. At the end of the washout period, patients restarted berberine or placebo twice a day for further 3 months. Anthropometric and metabolic parameters were assessed during the run-in period, at randomization, before and after the washout period.
Results: A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, Triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo.
Conclusions: Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.
Effect of Berberine Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
Background: The aim of this study was to evaluate the effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion.
Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with a diagnosis of metabolic syndrome. Glucose and insulin levels after a dextrose load were measured. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also measured. Twelve patients received berberine hydrochloride (500 mg) three times daily before meals for 3 months. The remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed.
Results: After berberine administration, patients had a remission of 36% (P=0.037) in the presence of metabolic syndrome and a significant decrease in waist circumference in females (106±4 vs. 103±3 cm, P<0.05), systolic blood pressure (SBP) (123±7 vs. 115±9 mmHg, P<0.01), Triglycerides (2.4±0.7 vs. 1.4±0.5 mmol/L, P<0.01), area under the curve (AUC) of glucose (1182.1±253.6 vs. 1069.5±172.4 mmol/l, P<0.05), AUC of insulin (92,056±72,148 vs. 67,407±46,441 pmol/L, P<0.01), and insulinogenic index (0.78±0.69 vs. 0.62±0.46, P<0.05), as well as an increase in the Matsuda index (2.1±1.0 vs. 3.1±1.6, P<0.01).
Conclusions: Administration of berberine leads to remission of metabolic syndrome and decreases in waist circumference, SBP, Triglycerides , and total insulin secretion, with an increase in insulin sensitivity.
Efficacy of berberine in patients with type 2 diabetes mellitus
Berberine has been shown to regulate glucose and lipid metabolism in vitro and in vivo. This pilot study was to determine the efficacy and safety of berberine in the treatment of type 2 diabetes mellitus patients. In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5% ± 0.5% to 7.5% ± 0.4%, P < .01), fasting blood glucose (from 10.6 ± 0.9 mmol/L to 6.9 ± 0.5 mmol/L, P < .01), postprandial blood glucose (from 19.8 ± 1.7 to 11.1 ± 0.9 mmol/L, P < .01), and plasma Triglycerides (from 1.13 ± 0.13 to 0.89 ± 0.03 mmol/L, P < .05) were observed in the berberine group. In study B, 48 adults with poorly controlled type 2 diabetes mellitus were treated supplemented with berberine in a 3-month trial. Berberine acted by lowering fasting blood glucose and postprandial blood glucose from 1 week to the end of the trial. Hemoglobin A1c decreased from 8.1% ± 0.2% to 7.3% ± 0.3% (P < .001). Fasting plasma insulin and homeostasis model assessment of insulin resistance index were reduced by 28.1% and 44.7% (P < .001), respectively. Total cholesterol and low-density lipoprotein cholesterol were decreased significantly as well. During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney damages were not observed for all patients. In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.
TRIB1 is a GWAS locus associated with plasma cholesterol and Triglycerides (TG) levels. In mice, liver-specific overexpression of TRIB1 lowers plasma lipid levels. Berberine (BBR) is a natural lipid lowering drug that reduces plasma LDL-cholesterol (LDL-C), total cholesterol (TC) and TG in hyperlipidemic patients and in mice by mechanisms involving upregulation of hepatic LDL receptor (LDLR). Here, we demonstrated that BBR treatment reduced plasma LDL-C, TC and TG in LDLR wildtype (WT) mice fed a high fat and high cholesterol diet and it only lowered TG in LDLR WT mice fed a normal chow diet. In hypercholesterolemic LDLR deficient mice (Ldlr−/−), BBR treatment reduced plasma TG levels by 51% compared to the vehicle control without affecting plasma cholesterol levels. Hepatic gene expression analysis revealed that Trib1 mRNA levels were significantly elevated by BBR treatment in all three mouse models and increases of Trib1 mRNA expression were associated with reduced expression of lipogenic genes including Cebpa, Acc1 and Scd1. In vitro studies further demonstrate that BBR induces TRIB1 mRNA expression by a transcriptional mechanism via ERK signaling pathway. These new findings warrant future in vivo studies to determine the causal role of Trib1 in BBR-mediated TG lowering independent of LDLR regulation.
Berberis lycium
Role of Berberis lycium inreducingserumcholesterol in Broilers
This study was planned to investigate the role of Berberis lycium inreducingserumcholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Averageserum totalcholesterol, Triglyceride ,high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average totalserumcholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Totalserumcholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Meanserum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Meanserum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05).serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The averageserumLDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively.LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed forreducingserum totalcholesterol, Triglyceride andLDL and increasing HDL.
Role of Berberis lycium in reducing serum cholesterol in broilers
This study was planned to investigate the role of Berberis lycium in reducing serum cholesterol in broilers. Six experimental rations designated as A, B, C, D, E and F having 0, 0.5, 1.0, 1.5, 2.0 and 2.5% Berberis lycium were fed to 240 broiler chicks, randomly distributed into 24 replicates, so as to have 4 replicates per group and 10 chicks per replicate. The experiment lasted for 35 days. Average serum total cholesterol, Triglyceride , high density lipoprotein (HDL) and low density lipoprotein (LDL) were used as criteria of response. Average total serum cholesterol per chick was 129.33, 120.50, 116.50, 113.00, 101.67 and 114.00 mg/dl for group A, B, C, D, E and F respectively. Total serum cholesterol showed decreasing trend with the increasing level of Berberis lycium unto 2% (p<0.05). Mean serum Triglyceride level per chick was 60.00, 58.17, 58.00, 55.33, 50.17 and 48.50 mg/dl for group A, B, C, D, E and F respectively. Mean serum Triglyceride showed decreasing trend with the increasing level of Berberis lycium (p<0.05). Serum Triglyceride was significantly lower in group F than other groups. Mean HDL per chick for the six experimental groups A, B, C, D, E and F was 52.08, 53.42, 60.42, 62.25, 62.92 and 54.50 mg/dl respectively. HDL showed increasing trend with the increase in the level of Berberis lycium unto 2%. The average serum LDL per chick was 65.25, 55.45, 44.48, 39.68, 28.72 and 49.80 mg/dl for group A, B, C, D, E and F respectively. LDL also showed decreasing trend with the increase in the level of Berberis lycium unto 2% (p<0.05). It was concluded that Berberis lycium added to feed at the rate of 2.0% can be used in broiler feed for reducing serum total cholesterol, Triglyceride and LDL and increasing HDL.
Effect of Berberis lycium Royle on Lipid Profile in Alloxan Induced Diabetic Rabbits
Berberis lycium Royle (B.l.R) commonly known as Ishkeen (Kashmal and Darbald) is widely used in folk medicines for the treatment of Diabetes mellitus. Experimental diabetes use to alter the lipid profile. The aim of the present study was to evaluate the effects of Berberis lycium root bark on various lipid profiles in alloxan induced diabetic rabbits. Diabetes was induced by single intravenous injection of Alloxan (150 mg/kg).Oral administration of 250mg/kg and 500mg/kg crude powder of Berberis lycium root for four weeks resulted in significant reduction in total cholesterol, Triglyceride and low density lipids (LDLs) levels. Berberis lycium treatment increased the levels of high density lipids (HDLs). Furthermore same doses stabilized the weight of diabetic rabbits. Thus our investigation clearly shows that crude powder of Berberis lycium Royle has antihyperlipidemic effect.
Hyperlipidemia is a condition in which blood is overloaded with lipids. This condition is challenging for living beings. There are many ways to solve this problem but herbal medicines
take on paramount importance in this regard. The purpose of the current research was to inspect the effects of an aqueous extract of Berberis lycium Royle root bark on lipid profiles of Swiss albino mice in which diabetic phenotype was induced by alloxan. A single injection of Alloxan (150 mg/kg) was applied intravenously to induce diabetic phenotype. Alloxan induction raised the overall level of Triglycerides , low density- lipids (LDLs), and cholesterol and reduced the level of high density lipids (HDLs). Oral administration of 200 mg/kg aqueous extract of B. lycium Royle root bark for 28 days rescued all these changes. This study shows that the root bark extract of B. lycium Royle has antihyperlipidemic properties.
Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects.
Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3–7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.
Chemistry and Biological Activities of Berberis lycium Royle
Berberis lycium Royle belonging to family Berberidaceae is a high-value medicinal plant with a known history of uses in folk medicine. It is used traditionally for curing a broad range of human illnesses and diseases in the Indian Himalayan region of Pakistan, India, and Bangladesh. Its ethnomedicinal uses include its use for treatment of jaundice, diabetes, eye infections, fractured bones, internal wounds, diarrhea, rheumatism, stomachache, and its use as a general body tonic. Although its every part has some medicinal properties, the most commonly used parts are roots and stem-bark. Its biologically active phytochemicals are alkaloids with berberine as the major one. An analysis of literature shows that its main biological activities are mainly attributed to berberine.Available literature shows that the plant has a wide range of biological activities including antihyperglycemic, antihyperlipidemic, anticancer and antitumor, wound and bone healing, antimicrobial, anticoccidial, antioxidant, hypotensive, immunity enhancing, antiurolithic, anthelmintic and hepatoprotective. Its wide use in folk medicine has prompted research in its phytochemical constituents and biological activities over the last four decades. Research in these lines is attesting its ethnomedicinal uses.This review paper is aimed to explore the chemistry and biological activities of this gifted medicinal plant.
Bergamot (Citrus bergamia)
The bergamot is a citrus fruit native to southern Italy with traditional uses that include improving immune response and cardiovascular function. There are a variety of phytochemicals that have been found in the bergamot including brutieridin and melitidin as well as other flavonoids, flavones O-glucosides and C-glucosides. Multiple clinical trials have provided evidence that different forms of orally administered bergamot can reduce totalcholesterol and low-density lipoproteincholesterol. In vitro mechanistic studies have provided evidence that polyphenols from the bergamot can alter the function of AMPK and pancreaticcholesterol ester hydrolase (pCEH). The use of bergamot in multiple clinical trials has consistently shown that it is well tolerated in studies ranging from 30 days to 12 weeks. This mini-review reports on the clinical studies performed with different forms of bergamot along with theireffectiveness inreducing totalcholesterol andLDLcholesterol in patients with hypercholesterolemia.
Backgrounds
Recent experiments suggest that Citrus bergamia extracts could benefit people with dyslipidemia and obesity but this needs to be further validated.
Methods
A total of 98 people age-matched older adults (65 years) with elevated blood lipids were enrolled to receive 12-week supplementation of a Citrus bergamia extracts-based formulation (CitriCholess)(n = 48) and placebo (n = 50).
Results
No group differences were found in baseline bodyweight, body mass index (BMI), blood cholesterol (TC), Triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and glucose levels. CitriCholess supplementation resulted in lower levels than placebo in TG (1.83 ± 0.92 vs. 1.95 ± 1.34 mmol/L, P = 0.612), TC (5.14 ± 0.98 vs. 5.44 ± 0.77 mmol/L, P = 0.097), and LDL-C (3.13 ± 0.74 vs. 3.43 ± 0.62 mmol/L, P = 0.032). Compared to placebo, CitriCholess also resulted in greater reductions in body weight (−0.604 ± 0.939 vs. 0.06 ± 0.74 kg, P < 0.01), waist circumferences (−0.60 ± 1.349 cm vs. -0.16 ± 1.503 cm, P < 0.01) and BMI (−0.207 ± 0.357 vs. 0.025 ± 0.274, P < 0.01). Additionally, females had a significantly higher level of HDL-C than males. TC was significantly correlated with LDL-C, and to a less degree, with TG. TG was inversely correlated with HDL-C. Body weight and waist circumference were negatively correlated with HDL-C and positively correlated with glucose.
Conclusion
12-week supplementation of CitriCholess could benefit lipid metabolism and weight management in old adults with dyslipidemia.
The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose Triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5′-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders.
The results of five different clinical trials (Table 1) using bergamot in various forms suggest the polyphenol fraction can lower LDL-C and total cholesterol. Several studies suggested that bergamot polyphenols can reduce Triglycerides and increase HDL-C, however, the results were not consistent across all studies. One possible explanation for this variability (i.e. TG and HDL-C) is that bergamot preparation, extraction, and standardization varied in several studies. Consistently in all of the clinical trials bergamot appeared to be well tolerated with studies ranging from 30 days to 6 months. There are several weaknesses in the design of several of the clinical trials that used an open label design (Table 1). However, it should be noted that each patient can serve as their own control since cholesterol was quantified prior to bergamot and at the completion of the study. Three of the studies suggested an increase in HDL by up to 4 mg/dl (Table 1). This is significant because HDL is often difficult to increase apart from lifestyle changes. Regarding the mechanism of action there are several possible mechanisms that may be responsible for improving cholesterol lab values including activation of AMPK and inhibition of pancreatic cholesterol ester hydrolase (pCEH). As of now the suggestions that bergamot inhibits HMG-CoA reductase appear to be largely based on molecular modeling and will require further studies to confirm this proposed mechanism of action. Taken together, these early clinical trials along with the mechanistic studies that have been performed suggest that bergamot can reduce total cholesterol and LDL-C through mechanisms that are distinct from current pharmaceutical approaches.
BACKGROUND:
The role of lipid-lowering and hypoglycemic nutraceuticals in cardiovascular disease prevention is the focus in recent years. The most studied compounds and plants are sterols, soy, red fermented rice, policosanols, artichoke, berberine. Epidemiological and experimental evidences suggest that dietary polyphenols, especially flavonoids, might play a role in preventing atherosclerosis, owing to their pleiotropic metabolic, anti-inflammatory and antioxidant effects. Recent studies have shown that bergamot juice and albedo (Citrus Bergamia Risso et Poiteau), an endemic plant growing in a limited part of the Ionian coast of Calabria (Italy) has a unique content of flavonoids and glycosides, such as neoeriocytrine, neoesperidine, naringenine, routine, neodesmine, polyphenol and poncirine.
OBJECTIVE:
The aim of this study was to investigate the effects of a phytocomplex from bergamot fruit (EP3116520A1) as dietary supplement to a Mediterranean diet on body weight, body mass index (BMI), waist circumference, plasmatic lipid fractions, glucose and C – reactive protein (CRP) in subjects with the metabolic syndrome (MetS; according to NCEP-ATP III criteria) without pharmacological treatment, exept for basic treatment.
METHODS:
80 overweight adults (54% females, 46% males) with the diagnosis of Metabolic Syndrome (MetS), aged 45 ± 5 years, were enrolled and randomized to 2 groups: group A) followed a personalized low calorie Mediterranean diet (control group) and group B) enriched the same diet therapy with 1 tablet of a phytocomplex from bergamot fruit per day for 6 months (intervention group).
RESULTS:
After 6 months patients in the intervention group showed a significant reduction of total cholesterol (–15% ), LDL-Cholesterol (–22% ), Triglycerides (–23% ), blood glucose (–15% ), CRP (–40% ) and a significant increase in the HDL-Cholesterol (+ 14% ) levels compared to the control group (diet alone) where the changes were not significant, with not much significance in reduced body weight.
CONCLUSION:
Our findings suggest that bergamot supplementation improves significantly all aspects of metabolic profile in patients with MetS and is superior to diet alone.
Elevated serum cholesterol, Triglycerides and LDL levels are often associated with an increased incidence of atherosclerosis and coronary artery disease. The most effective therapeutic strategy against these diseases is based on statins administration, nevertheless some patients, especially those with metabolic syndrome fail to achieve their recommended LDL targets with statin therapy, moreover, it may induce many serious side effects. Several scientific studies have highlighted a strong correlation between diets rich in flavonoids and cardiovascular risk reduction. In particular, Citrus bergamia Risso, also known as bergamot, has shown a significant degree of hypocholesterolemic and antioxidant/radical scavenging activities. In addition, this fruit has attracted considerable attention due to its peculiar flavonoid composition, since it contains some flavanones that can act as natural statins. Hence, the study of bergamot flavonoids as metabolic regulators offers a great opportunity for screening and discovery of new therapeutic agents. Cholesterol metabolism, flavonoid composition and potential therapeutic use of C. bergamia Risso will be discussed in the following review.
black Cumin seeds (Nigella sativa L.)
Use of black cumin in layerdiet ascholesterollowering agents in egg yolk
This study was conducted to investigate theeffects of different levels of black cumin seeds (Nigella
sativa L.) on egg production andcholesterol concentration in egg yolk of laying hens. A total of 60
commercial layer strain day old layer chicks were collected and divided into three groups treated with
1.0%, 1.5% and 2.0% black cumin inclusion. The concentrations of totallipids, totalcholesterol,
phospholipids and triacylglycerols inserum and egg yolk were measured. Feeding of thediets with
1%, 1.5% and 2% black cumin seeds during the laying period found egg yolkcholesterol by 11.12,
9.88 and 9.83 mg/g respectively. The results found that feed efficiency ratio, egg production, body
weight, feed intake and egg weight were nonsignificant between the treatments. However, egg yolk
cholesterol concentration was found that 1.5% and 2.0% black cumin indiet were reducedcholesterol
concentration insignificance (P<0.05). So, dried black cumin supplementation indiets had no any
adverseeffect on egg production and egg weight. Furthermore, egg yolkcholesterol concentrations
were decreased. Hence, it is concluded that black cumin (Nigella sativa L.) seeds and/or the active
principle are of interest as potential egg-yolkcholesterol-lowering agents.
The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and Triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and Triglyceride levels (WMD: -20.64mg/dL, 95% CI: -30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes.
The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane’s Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: −16.80; 95% CI: −21.04, −12.55), Triglycerides (WMD: −15.73; 95% CI: −20.77, −10.69), LDL-cholesterol (WMD: −18.45; 95% CI: −22.44, −14.94) and VLDL-cholesterol (WMD: −3.72; 95% CI: −7.27, −0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: −15.18; 95% CI: −19.82, −10.55) and HbA1C levels (WMD: −0.45; 95% CI: −0.66, −0.23). Effects of N. sativa on CRP (WMD: −3.61; 95% CI: −9.23, 2.01), TNF-α (WMD: −1.18; 95% CI: −3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: −0.95; 95% CI: −2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, Triglycerides , total-, VLDL-, LDL-cholesterol levels.
Effect of Nigella Sativa on Lipid Profile in Albino Rats
Background: Coronary heart disease is a global health problem. Dyslipidemia is one of its major risk factors. The purpose of this study was to assess the effect of Nigella sativa seeds in the diet on lipid profile in albino rats.
Material and methods: Eighty-four albino rats were divided into six groups. Control groups I, III and V were given; low fat diet with 3% sunflower oil, high fat diet with 20% sunflower oil and high fat diet supplemented with 1% colic acid and 0.5% propylthiouracil as atherogenic elements respectively. The Experimental groups II, IV and VI were given above diets respectively supplemented with Nigella sativa seeds. Lipid profile was estimated at 0, 12 and 24 weeks.
Results: Albino rats fed on low fat diet containing 3% sunflower oil supplemented with Nigella sativa showed significant reduction in TC and LDL cholesterol and rise in HDL cholesterol. Those on high fat diet containing 20% sunflower oil with Nigella sativa seeds showed significant reduction in TG and LDL cholesterol and increase in HDL cholesterol. While in those given high fat diet with 20% sunflower oil, along with 1% cholic acid and 0.5% propylthiouracil with the addition of Nigella sativa, there was significant reduction in TC and LDL cholesterol and rise in HDL cholesterol.
Conclusion: Nigella sativa seeds in the diet has a favorable effect on lipid profile by lowering the Triglyceride , total cholesterol and LDL cholesterol and increasing the HDL cholesterol in albino rats.
Ameliorative effects of Nigella sativa on dyslipidemia
Introduction
Dyslipidemia is an established risk factor for ischemic heart disease. Nigella sativa (NS) is a medicinal plant that has been used for the treatment and prevention of a variety of diseases, in particular hyperlipidemia.
Methods
We reviewed the existing literature published until 2014 by using the following keywords: ‘‘Nigella sativa’’, ‘‘black cumin’’, ‘‘black seeds’’, ‘‘thymoquinone’’, and ‘‘lipid’’.
Results
In the conducted studies, different preparations of NS including seed powder (100 mg–20 g daily), seed oil (20–800 mg daily), thymoquinone (3.5–20 mg daily), and seed extract (methanolic extract especially), were shown to reduce plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and Triglycerides , but the effect on high-density lipoprotein cholesterol (HDL-C) was not significant. NS and thymoquinone have been reported to be safe and well tolerated with no severe adverse effect. In clinical trials, NS was found to be effective when added as adjunct to standard antihyperlipidemic and antidiabetic medications. Lipid-modifying effects of NS could be attributed to the inhibition of intestinal cholesterol absorption, decreased hepatic cholesterol synthesis, and up-regulation of LDL receptors.
Conclusions
Overall, the evidence from experimental and a clinical studies suggests that NS seeds are a promising natural therapy for dyslipidemic patients.
Nigella sativaprovides protection against metabolic syndrome
The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II (Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum Triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia.
The aim of the present study was to determine the effects of Nigella sativa (NS) oil on glucose metabolism and lipid concentrations in patients with type 2 diabetes (T2DM). In this double-blind randomized controlled clinical trial, 72 volunteer subjects at Endocrinology Clinics of Kermanshah were recruited. Participants were patients aged 30–60 years old with T2DM. They were randomly divided into intervention (n = 36) and placebo groups (n = 36) and received 3 g/day (one three times a day) NS oil or sunflower soft gel capsules for 12 weeks. At baseline and at the end of the trial, anthropometric indices, dietary intake and biochemical parameters were measured. Sixty-seven patients completed the trial (intervention n = 34, placebo n = 33). Since the data analysis was based on intention-to-treat approach, all 72 subjects (36 in each group) were included for data analysis. Two groups were similar in the baseline characteristics. After the intervention, weight and body mass index decreased in the intervention group compared to the baseline, but it was not significant between the two groups. Dietary intake in both groups changed compared to baseline. Comparison of the two groups indicated that fasting blood sugar, glycated hemoglobin, Triglyceride and low density lipoprotein–cholesterol changed significantly in intervention group compared to the placebo group (p < 0.05, adjusted for confounder factors). Insulin level and insulin resistance decreased and high density lipoprotein–cholesterol increased in the intervention group, but after adjusting for confounder factors, they were not significant. Supplementation with NS oil can improve glycemic status and lipid profile in patients with T2DM.
Blackcurrant (Ribes nigrum) Extract
Blackcurrant extract (BCE)ameliorates dyslipidemia in menopausal model animals and in elderly women at a risk of dyslipidemia. However, it is unknown whether the daily intake of BCE can preventlipid abnormalities in healthy individuals.lipids are essential for the body, but they also cause arteriosclerosis. In this noncomparative pilot study, we examined theeffects of BCE administered for 29 days onserumlipids in young healthy women.blood samples were collected before and on days 4 and 29 after BCE intake, and 20 lipoprotein fractions in theserum were separated using a gel-permeationhigh-performance liquid chromatography method to measure the triacylglycerol andcholesterol levels in lipoproteins. There were noeffects onlipids on day 4 of BCE intake, but the totalcholesterol level decreased on day 29. Furthermore, the levels of total very-low-density lipoprotein (VLDL)cholesterol, small VLDLcholesterol, and large low-density lipoproteincholesterol were significantly decreased. These results suggest that the daily intake of BCE has ahypocholesterolemiceffect in healthy women, and that it iseffective in preventingAtherosclerosis.
Purposes: We previously showed that polyphenol-rich blackcurrant extract (BCE) showed ahypocholesterolemiceffect in mice fed ahigh fatdiet. As directcholesterol removal from the body via the intestine has been recently appreciated, we investigated theeffect of BCE on the modulation of genes involved in intestinalcholesteroltransport using Caco-2 cells as an in vitro model.
Methods: Caco-2 cells were treated with BCE to determine itseffects on mRNA and protein expression of genes important for intestinalcholesteroltransport, low-density lipoprotein (LDL) uptake, cellularcholesterol content, andcholesteroltransport from basolateral to apical membrane of Caco-2 cell monolayers. Cells were also treated with anthocyanin-rich or -poor fraction of BCE to determine the role of anthocyanin on BCEeffects.
Results: BCE significantly increased protein levels ofLDL receptor (LDLR) without altering its mRNA, which consequently increasedLDL uptake into Caco-2 cells. This post-transcriptional induction ofLDLR by BCE was markedly attenuated in the presence of rapamycin, anInhibitor of mechanistic target of rapamycin complex 1 (mTORC1). In addition, BCE altered genes involved incholesteroltransport in the enterocytes, including apical and basolateralcholesteroltransporters, in such a way that could enhancecholesterol flux from the basolateral to apical side of the enterocytes. Indeed, BCE significantly increased the flux ofLDL-derivedcholesterol from the basolateral to the apical chamber of Caco-2 monolayer.LDLR protein levels were markedly increased by anthocyanin-rich fraction, but not by anthocyanin-free fraction.
Conclusion: mTORC1-dependent post-transcriptional induction ofLDLR by BCE anthocyanins drove thetransport ofLDL-derivedcholesterol to the apical side of the enterocytes. This may represent a potential mechanism for thehypocholesterolemiceffect of BCE.
Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of Triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract’s high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.
Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (Ribes nigrum L.) extract (BCE) had phytoestrogen activity. In this study, we examined whether BCE improved lipid metabolism abnormalities and reduced liver steatosis in ovariectomized rats, as a menopausal animal model. Twelve-week-old ovariectomized (OVX) rats were fed a regular diet (Ctrl) or a 3% BCE supplemented diet while sham rats were fed a regular diet for three months. Body weight, visceral fat weight, levels of serum Triglycerides , total cholesterol, and LDL cholesterol decreased in the BCE-treated OVX and sham rats, but not in OVX Ctrl rats. The results of hematoxylin and eosin staining revealed that BCE decreased the diameters of adipocytes and the nonalcoholic fatty liver disease activity score. Furthermore, quantitative RT-PCR indicated a decreased expression of hepatitis-related genes, such as tumor necrosis factor-α, IL-6, and IL-1β in OVX rats after BCE treatment. This is the first study that reported improvement of lipid metabolism abnormalities in OVX rats by BCE administration. These results suggest that the intake of BCE alleviated dyslipidemia and prevented nonalcoholic steatohepatitis during menopause in this animal model.
Bulbus Allii Macrostemonis extract
Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level.
Bupleurum scorzonerifolium Willd.root extract
The aim of this study was to investigate the antiobesity and antihyperlipidemiceffects of vinegar-baked Radix Bupleuri (VBRB) onhigh-fatdiet- (HFD-) induced obese rats. After being fed HFD for two weeks, rats were dosed orally with VBRB or fenofibrate, once daily for further twelve weeks. VBRB (1.0 g kg−1 per day) producedeffects similar to fenofibrate (100 mg kg−1) inreducing body weight (BW) gain, visceral fat-pad weights, plasmalipid levels, as well as hepatic Triglyceride andcholesterol content of HFD-fed rats. VBRB also lowered hepaticlipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. VBRB and fenofibratereversed the HFD-induced downregulation of hepatic peroxisome proliferator-activated receptor (PPAR)α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) proteins werereversed by VBRB and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats was lowered by VBRB and fenofibrate. The results of this study show that VBRB suppresses BW gain and body fat accumulation by increasing fatty acid oxidation, aneffect which is likely mediated via upregulation of PPARα and downregulation of SREBP expression in the liver of HFD-fed rats.
Saikosaponinsameliorate hyperlipidemia in rats by enhancing hepaticlipid andcholesterol metabolism
Abstract
Ethnopharmacological relevance
Hyperlipidemia is the systemic manifestation of abnormallipidmetabolism, characterized by elevated circulating levels ofcholesterol and Triglyceride and ahigh risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB,ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemiaeffects and plausible underlying mechanisms remain elusive.
Aim of the study
To comprehensively evaluate thelipid-lowering potential of SSs against hyperlipidemia in rats.
Materials and methods
RNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome andserumlipid profile in long-termhigh-fatdiet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention.
Results
Our data revealed that SSs significantly alleviated HFD-inducedhyperTriglyceride mia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalancedbloodlipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulatedcholesterol clearance by promoting intracellularcholesterolefflux, HDL remodeling,LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver fromlipid overload-related oxidative stress andlipid peroxidation, as well as substantially exaggerated inflammatory response.
Conclusion
Our research not only unraveled the intricate mechanisms underlying thelipid-lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia.
C. pinnatifida Bge fruit Flavones
Theeffects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity,highblood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacologicaleffects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL)cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficialeffects on controlling and treatinghighblood sugar, dyslipidemia, obesity andAtherosclerosis. The aim of this review is tohighlight the interestingeffects of C. pinnatifida on metabolic syndrome.
A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of Triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.
Caesalpinia gilleisii Wall et Hook extract
Caesalpinia ferrea C. Mart. (Fabaceae) Phytochemistry, Ethnobotany, and Bioactivities: A Review
Caesalpinia ferrea C. Mart., popularly known as “Jucá” or “Pau-ferro”, belongs to the Fabaceae family, and is classified as a native and endemic species in Brazil. Numerous studies that portray its ethnobotany, chemical composition, and biological activities exist in the literature. The present study aimed to systematically review publications addressing the botanical aspects, uses in popular medicine, phytochemical composition, and bioactivities of C. ferrea. The searches focused on publications from 2015 to March 2020 using the Scopus, Periódicos Capes, PubMed, Google Scholar, and ScienceDirect databases. The leaves, fruits, seeds, and bark from C. ferrea are used in popular medicine to treat disorders affecting several systems, including the circulatory, immune, cardiovascular, digestive, respiratory, genitourinary, musculoskeletal, and conjunctive systems. The most commonly found chemical classes in phytochemical studies are flavonoids, polyphenols, terpenoids, tannins, saponins, steroids, and other phenolic compounds. The biological properties of the extracts and isolated compounds of C. ferrea most cited in the literature were antibacterial, antifungal, antioxidant, antiproliferative, anti-inflammatory, and healing potential. However, further studies are still needed to clarify a link between its traditional uses, the active compounds, and the reported pharmacological activities, as well as detailed research to determine the toxicological profile of C. ferrea.
Caparis decidua. fruit extract
Antiatheroscleroticeffect of Caparis decidua. Fruit Extract incholesterol-fed Rabbits
The fruit alcohol extract of the plant Capparis decidua (Frosk.).. Edgew was investigated for itsAntiatherosclerotic activity. Hyperlipidemia was induced by atherodiet andcholesterol feeding to animals. Rabbits were fed Capparis decidua. (500 mg/kg body weight) or pitavastatin (0.2 mg/kg body weight) in distilled water along with standard laboratorydiet and atherodiet for 60 days. C. decidua. fruit extract and pitavastatin were found to lowerserumcholesterol,LDL-cholesterol, Triglyceride , phospholipid, and atherogenic index, but found to increase the HDL to totalcholesterol ratio as compared with hyperlipidemic control group. Pitavastatin or C. decidua. fruit extract treated hyperlipidemic rabbits showed a decrease in thelipid profile of liver, heart, and aorta. The plant extract feeding brings about a definite regression of atheroma and hindered plaque formation in aorta as compared with the hyperlipidemic control group. Thus, this study demonstrates that C. decidua. fruit extract possesseshypolipidemic andAntiatheroscleroticeffects.
Free fatty acids regulating action of Capparis decidua fruit on dyslipidemia in rats
Capparis decidua belongs to family Capparidaceae in wastelands of India. The study aim was to determine the role of C. decidua fruits on the free fatty acids (FFA) profile in fat-rich diet (FRD) dyslipidemic rats. The methanolic extract of edible fruit of C. decidua (CD) was given orally to obese dyslipidemic rats at the dose of 125 mg/kg and 250 mg/kg for consecutive 28 days. CD treatment in FRD rats significantly restricts the body weight gains. Blood lipid profile was altered dose dependently and significantly after 4-week treatment with CD to FRD. rats. It significantly (p<0.05) enhanced serum FFA especially, -linolinate, -linolinate, arachidonate, ecosapentaenoate, docosapentaenoate and docosahexaenoate. Moreover, 3-PUFA content was also enhanced (50.3% and 78.8%) in the serum of CD treated animals, whereas MUFA was lowered (31.1% and 40%). Therefore, Capparis decidua fruit has a promising role on dyslipidemia and obesity and has the capabilities to regulate beneficial free fatty acids. .
Caralluma fimbriata extract
Antiobesogenic andAntiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. Thediet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigeniceffects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteriadiet (CA), and (iii) cafeteriadiet fed + CFE treated. Rats in the test group received cafeteriadiet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogeniceffects of CFE were evaluated by monitoring changes in feed intake, body weight,serumlipid and hormonal (leptin) profiles, fat pads, and liver weight.Antiatheroscleroticeffects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations inserumlipid profiles associated with weight gain were similarly inhibited, as were the typical increases inserum leptin levels. These data substantiate CFE’s reported anorexigeniceffects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic andAntiatherosclerotic properties.
The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200 mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20 mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90 days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL-cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p < 0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption.
Antiobesogenic and Antiatherosclerotic Properties of Caralluma fimbriata Extract
There is evidence that the principles present in the widely consumed Indian food plant C. fimbriata extract (CFE) suppress appetite, and provide antiobesogenic and metabolic benefits. The Diet-Induced Obesity (DIO) rat model was used to investigate CFE’s anorexigenic effects. Rats were randomly divided into three groups: (i) untreated control (C), (ii) control for cafeteria diet (CA), and (iii) cafeteria diet fed + CFE treated. Rats in the test group received cafeteria diet and CFE from day one onwards. CFE was administered by gavage at three doses (25, 50, 100 mg/Kg BW per day) for 90 days. The antiobesogenic effects of CFE were evaluated by monitoring changes in feed intake, body weight, serum lipid and hormonal (leptin) profiles, fat pads, and liver weight. Antiatherosclerotic effects were measured by histology. CFE induced significant and dose-dependent inhibition of food intake, with dose-related prevention of gains in body weight, liver weight, and fat pad mass. Alterations in serum lipid profiles associated with weight gain were similarly inhibited, as were the typical increases in serum leptin levels. These data substantiate CFE’s reported anorexigenic effects. CFE treatment also conferred protection against atherogenesis. We conclude that CFE possesses antiobesogenic and antiatherosclerotic properties.
Carnosic Acid (Rosmarinus officinalis)
Rosemary (Rosmarinus officinalis L.) extracts (RE) are natural antioxidants that are used in food, food supplements and cosmetic applications; exert anti-inflammatory and anti-hyperglycaemiceffects; and promote weight loss, which can be exploited to develop new preventive strategies against metabolic disorders. Therefore, the aim of the present study was to evaluate the preventiveeffects of rosemary leaf extract that was standardised to 20 % carnosic acid (RE) on weight gain,glucose levels andlipid homeostasis in mice that had begun ahigh-fatdiet (HFD) as juveniles. The animals were given a low-fatdiet, a HFD or a HFD that was supplemented with 500 mg RE/kg body weight per d (mpk). Physiological and biochemical parameters were monitored for 16 weeks. Body and epididymal fat weight in animals on the HFD that was supplemented with RE increased 69 and 79 % less than those in the HFD group. Treatment with RE was associated with increased faecal fat excretion but not with decreased food intake. The extract also reduced fasting glycaemia and plasmacholesterol levels. In addition, we evaluated theInhibitoryeffects of RE in vitro on pancreatic lipase and PPAR-γ agonist activity; the in vitro findings correlated with our observations in the animal experiments. Thus, the present results suggest that RE that is rich in carnosic acid can be used as a preventive treatment against metabolic disorders, which merits further examination at physiological doses in randomised controlled trials.
Carnosic acid, a new class of lipid absorption inhibitor from sage
The methanolic extract from the leaves of Salvia officinalis L. (sage) showed significant inhibitory effect on serum Triglyceride elevation in olive oil-loaded mice (500 and 1000 mg/kg, p.o.) and inhibitory activity (IC(50): 94 microg/mL) against pancreatic lipase, which is participated in digestion of lipids. Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction. Among these compounds, carnosic acid and carnosol substantially inhibited pancreatic lipase activity with IC(50) values of 12 microg/mL (36 microM) and 4.4 microg/mL (13 microM), respectively. Carnosic acid significantly inhibited Triglyceride elevation in olive oil-loaded mice at doses of 5-20 mg/kg (p.o.). However, other constituents (carnosol, royleanonic acid, oleanolic acid) did not show any effects at a dose of 200 mg/kg (p.o.). Furthermore, carnosic acid (20 mg/kg/day, p.o.) reduced the gain of body weight and the accumulation of epididymal fat weight in high fat diet-fed mice after 14 days.
Carnosic acid prevents obesity and hepatic steatosis in ob/ob mice
Aim: Carnosic acid (CA) inhibits adipogenesis in vitro. The present study evaluated the therapeutic effects of CA in ob/ob mice.
Methods: The experimental animals were given a standard chow diet with or without CA for 5 weeks. Bodyweight gain and food intake were measured during this period. Magnetic resonance imaging analysis, histological examination, serum chemistry analysis and intraperitoneal glucose tolerance test (IPGTT) were all performed.
Results: The mice fed CA experienced significant weight loss and reduced visceral adiposity, in addition to significantly reduced serum Triglyceride (TG) and cholesterol levels. Importantly, CA had a dramatic effect on the liver by reducing the hepatic TG content, thus decreasing serum alanine aminotransferase levels. In addition, IPGTT revealed that CA significantly improved glucose tolerance.
Conclusion: These data suggest that CA is a novel therapeutic agent for obesity-related non-alcoholic fatty liver disease.
Carthamus tinctorius extract
FBS, Triglyceride, cholesterol, LDL-C and VLDL-C had a meaningful decrease in diabetic rats treated with Carthamus tinctorius and diabetic rats treated with glibenclamide as compared with diabetic rats with no treatment. Insulin level increased significantly in diabetic groups received treatment (glibenclamide or Carthamus tinctorius L) in comparison with diabetic group with no treatment. The histological study revealed size of islets of Langerhans enlarged significantly consequentially as compared with diabetic rats with no treatment. The extract appeared non toxic as evidenced by normal levels of AST, ALP and ALT. Effects of administrating glibenclamide or extract of Carthamus tinctorius L on all biochemical parameters discussed above showed no difference and both tend to bring the values to near normal.
Cashew leaves (Anacardium occidentale)
Cashew leaves (Anacardium occidentale) is a medicinal plant applied in the treatment of some non-scientific claims of common diseases in SouthWestern Nigeria such as hypertension. It contains phytochemicals such as Phenolic, flavonoids, steroids, triterpenes and 33.52% to 46.26% ofdietary fiber. This work was therefore designed to determine thecholesterolloweringeffect of Cashew leaf (Anacardium occidentale) extract on Egg Yolk Induced Hypercholesterolaemic Rabbits. Fifteen rabbits classified into control group A of five rabbits; experimental group B induced with hypercholesterolemia using 20% egg yolk(B1) and thereafter given cashew leaf ethanolic extract(B2) and group C of five rabbits induced with hypercholesterolemia using 20% egg yolk(C 1) thereafter treated with the aqueous extract of cashew leaf(C 2). Outcomes of biochemical evaluation of experimental rabbits were compared with the control rabbits. Plasma Totalcholesterol(CHOL-T), Low Density Lipoprotein-cholesterol(LDL-C),Total Triglycerides (TG-T),high Density Lipoprotein-cholesterol (HDL-C) were evaluated in the rabbits by autoanalysis using ROCHE reagent on COBAS C111 autoChemistry analyzer. There was a significant increase in plasma totalcholesterol,LDL-C, total Triglycerides and HDL-C when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days compared with control rabbits fed on normaldiet and water for 7 days with p<0.05. A significant decrease was also obtained in plasma Totalcholesterol and Total Triglycerides in the rabbits given 400mg/Kg of either ethanolic or aqueous extract of cashew leaves extract after they were being given 20% of powdered egg yolk of the total meal weight plus water for seven days which was more in ethanolic extract than the aqueous extract with p<0.05. There was also a significantly lowerLDL-C in rabbits fed with normal meal containing 20% of powdered egg yolk of the total meal weight plus water for seven days followed by the administration of 400mg/Kg of ethanolic extract for another seven days. than when the rabbits were fed with normal meal containing 20% of powdered egg yolk of the total meal weight with water for seven days and also than in the rabbits induced with hypercholesterolemia using20% of powdered egg yolk of the total meal weight followed by aqueous cashew leaf extract (p<0.05). This work revealed the efficacy of 20% egg yolk at inducing hypercholesterolaemia while ethanonolic and aqueous extract have been found to decrease plasma levels of CHOL-T, TG-T andLDL-C and as such could be applied in the treatment of hypertecholesterolaemia which may result into hypertension.
Extract of the Anacardium occidentale leaves is used in the traditional treatment of diabetic diseases. The hypoglycemic effect of leaves aqueous extract was investigated using normoglycemic albino rats. The leaves aqueous extract was found to contain phytochemicals such as alkaloids, saponins, flavonoids and tannins. The aqueous extract significantly lowered the blood glucose concentration in the normal rats (p> 0.05). The extract produced about 33.7 % (305 ± 2.89 to 202 ± 4.04) mg/dl. The serum Triglyceride decreases by 48.28 % (435± 4.50 to 225 ± 1.50) mg/dl in the experimental rats. While serum total protein decreases by 18.41% (27.7 ± 2.54 to 22.6 ± 0.32) g/d and weight increase was 4.75 % (134.6 ± 5.02 to 128.5 ± 1.15) g. The result obtained indicated that the extract has a moderate hypoglycemic effect and may be used locally for the treatment of diabetes mellitus.
Celastrus Orbiculatus Thunb.
Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed ahigh-fatdiet, and increaseshigh-density lipoprotein (HDL). In the present study, we investigated theeffect of COT inreducinglipid accumulation and promotingreversecholesteroltransport (RCT) in vivo and vitro. Healthy male mice were treated withhigh-fatdiet alone,high-fatdiet with COT (10.0 g/kg/d), or general fodder for 6 weeks.serum levels of totalcholesterol (TC), Triglyceride (TG), HDL-C, non-HDL-C, and 3H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and Triglyceride in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reducedlipid accumulation in the liver,ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C andapolipoprotein A (apoA1). 3H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1,LDLR, ATP-binding cassettetransporters ABCA1, ABCG5, and LXRα wereimproved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased theefflux of 3H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT inreducinglipid accumulation by promoting RCT. Theseeffects may be achieved by activating the SRB1 and ABCtransporter pathway and promotingcholesterolmetabolism via the CYP7A1 pathway in vivo. Theeffective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.
Celastrus orbiculatus Thunb. (COT) is a traditional Chinese herb. In this study, an experiment was designed to investigate the potential protective effect of COT on the development of non-alcoholic fatty liver disease (NAFLD) induced by high fat diet and to explore the underlying mechanisms. We established a guinea pig model of NAFLD and treated the animals with three doses of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. H&E staining of liver tissue sections indicated that COT remarkably improved histopathological change of liver induced by high fat diet. Serum biochemical assays revealed that COT significantly decreased ALT and AST activities in serum. Besides, COT also reduced body weight and liver weight of guinea pigs under high fat diet. Hepatic lipid analysis showed that COT remarkably decreased the contents of total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and Triglyceride (TG) in liver of guinea pigs fed high fat diet in a dose-dependent manner. The analysis of hepatic genes involved in cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of cholesterol 7alpha-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Measurement of biochemical parameters in liver indicated that COT attenuated oxidative stress and lowered NO and iNOS levels in guinea pigs under high fat diet. These results reveal that administration of COT effectively ameliorates high-fat diet-induced NAFLD in guinea pigs through decreasing hepatic lipid levels, suppressing oxidative stress and lowering NO and iNOS levels in liver.
chalcone derivative, 1m-6
Background and Purpose
Atherosclerosis, resulting fromlipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotectiveeffects. We aimed to develop aneffective chalcone derivative with antiatherogenic potential.
Experimental Approach
Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. Thecholesterolefflux capacity was assayed by 3H labelling ofcholesterol.LDL receptor knockout (LDLR−/−) mice fed ahigh-fatdiet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation.
Key Results
Using ATP-binding cassettetransporter A1 (ABCA1) expression we identified the chalcone derivative, 1m-6, which enhances ABCA1 expression and promotescholesterolefflux in THP-1 macrophages. Moreover, 1m-6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1-regulating miRNAs through nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1) signalling. Additionally, 1m-6 significantly inhibits TNF-α-induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO-1 signalling in HUVECs. InAtherosclerosis-prone mice, 1m-6 significantly reduceslipid accumulation and atherosclerotic plaque formation.
Conclusion and Implications
Our study demonstrates that 1m-6 produces promising atheroprotectiveeffects by enhancingcholesterolefflux and suppressing inflammation-induced endothelial dysfunction, which opens a new avenue for treating ASCVD.
Chenodeoxycholic acid (CDCA)
Background: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepaticcholesterol and bile acid synthesis and reduces biliarycholesterol secretion and Triglyceride production. Animal studies have shown that bile acids downregulate hepaticLDL receptors (LDLRs); however, information onLDLmetabolism in humans is limited.
Methods: Kinetics of autologous 125 I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg-1 day-1 ). In seven patients with gallstones treated with CDCA for 3 weeks before cholecystectomy, liver biopsies were collected and analysed for enzyme activities and for specificLDLR binding.serum samples obtained before treatment and at surgery were analysed for markers oflipidmetabolism, lipoproteins and theLDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9).
Results: Chenodeoxycholic acid treatment increased plasmaLDLcholesterol by ~10% as a result of reduced clearance of plasmaLDL-apolipoprotein (apo)B;LDL production was somewhat reduced. The reduction inLDL clearance occurred within 1 day after initiation of treatment. In CDCA-treated patients with gallstones, hepatic microsomalcholesterol 7α-hydroxylase and HMG-CoA reductase activities were reduced by 83% and 54%, respectively, and specificLDLR binding was reduced by 20%. During treatment,serum levels of fibroblast growth factor 19 and total andLDLcholesterol increased, whereas levels of 7α-hydroxy-4-cholesten-3-one, lathosterol,PCSK9, apoA-I, apoC-III, lipoprotein(a), Triglycerides and insulin were reduced.
Conclusions: Chenodeoxycholic acid has a broad influence onlipidmetabolism, includingreducing plasma clearance ofLDL. The reduction in circulatingPCSK9 may dampen itseffect on hepaticLDLRs and plasmaLDLcholesterol. Further studies of theeffects of other FXR agonists oncholesterolmetabolism in humans seem warranted, considering the renewed interest for such therapy in liver disease and diabetes.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Theeffects on biliarylipids of 10 mg per kg per day of chenodeoxycholic acid (CDCA), 10 mg per kg per day of ursodeoxycholic acid (UDCA), and their equimolar combination (5 mg per kg per day of each), all administered for 45 to 60 days, were investigated in 18 patients with gallstones in a double-blind study with a balanced latin square design. The molar percentage ofcholesterol in bile (initial value 9.7 ± 2.2) was significantly lower after UDCA (5.4 ± 1.3) and the combination (5.2 ± 1.2) than after CDCA (7.2 ± 1.7).
Nevertheless, when the ability to solubilizecholesterol was calculated, taking into account the percentage of biliary UDCA, then the differences incholesterol saturation induced by UDCA alone and the combination also became considerable (saturation index: 0.94 ± 0.12 as compared to 0.81 ± 0.12).
The total bile acid pool increased significantly after treatment with CDCA and the combination, but not after UDCA. Lithocholic acid was increased significantly only by treatment with CDCA.
Diarrhea was observed in five patients with hypertransaminasemia and in four patients after CDCA, whereas both UDCA and the combination were well-tolerated.
We conclude that the administration of a combination of equimolar doses of CDCA and UDCA can be recommended for medical treatment of gallstones since it has greatereffects on bilecholesterol saturation than either alone, is better tolerated than CDCA, and is less expensive than UDCA.
The effects of chenodeoxycholic acid (C.D.C.A.) therapy on plasma lipid and lipoprotein metabolism have been studied in eleven patients with hypertriglyceridæmia. Plasma-Triglycerides fell significantly by 79-986 mg. per 100 ml. (25-54%) in nine of the patients, the absolute fall being positively correlated with the pretreatment concentration. The Triglyceride -lowering effect of C.D.C.A. appeared to derive from a decreased secretion into plasma of the Triglyceride -rich very-low-density lipoprotein. Three patients also demonstrated relatively smaller falls (14-28%) in plasma-cholesterol. Treatment was well tolerated, although in nine patients the serum activities of aspartate and alanine amino-transferases rose slightly. Long-term clinical trials of C.D.C.A. in the treatment of hypertriglyceridæmia seem to be indicated.
Chenodeoxycholic acid therapy for hypertriglyceridaemia in men
Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum Triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and thereafter monthly for a further 6 months on clofibrate 2 g daily. 2 The mean serum Triglyceride level fell by 36% after dietary treatment alone (P less than 0.05) and by 47% from initial values on diet plus chenodeoxycholic acid (P less than 0.01). In the nine patients who proceeded to clofibrate therapy there was a rise in Triglyceride levels on placebo capsules to the level achieved by diet alone, and a further fall on diet plus clofibrate of 47% of initial values (P less than 0.05). 3 Chenodeoxycholic acid therapy is effective in the management of hypertriglyceridaemia not completely cured by dietary measures, and may be as efficacious as clofibrate.
Chinese Taxillus Twing extract
Chinese medicinal composition for treating hyperlipidemia
Chinese angelica nourishes blood and invigorates blood circulation; the szechwan lovage rhizome dredges meridians and removes stasis; the safflower invigorates blood circulation and removes stasis; the peach kernel breaks blood and removes stasis, and relaxes bowl; the zedoary can promote the circulation of qi and remove stasis in blood; and the combined application of the medicaments can make total cholesterol (TC) and/or Triglyceride (TG) or high-density lipoprotein cholesterol (HDL-C) in the blood within the range of normal values so as to ensure that the metabolism or operation of blood fat is normal.
Chitosan
This study presents a meta-analysis of studies that investigate theeffectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate theeffect of chitosan supplementation. Theeffect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity ofeffect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity ofeffect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated,blood Triglyceride and HDL-cholesterol showed thehighest heterogeneity, respectively. Other thanblood HDL-cholesterol, totalcholesterol, and Triglyceride in feces, most items evaluated showed a negativeeffect size withhigh significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be mosteffective inlowering body weight. In addition, chitosan supplementation proved to be aneffective solution forserum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise inreducing the risk ofcholesterol related metabolic disorder.
Properties of nanopowdered chitosan and itscholesterolloweringeffect in rats
This study was carried out to compare the properties of nanopowdered chitosan (NPC) to commercially powdered chitosan (CPC) and examine theeffect of NPC onserum and livercholesterollowering in rats. Twentyfour male rats of Sprague-Dawley strain were blocked into 3 groups and were raised for 8 weeks.highcholesteroldiet, 2% CPC, or 2% NPC were given to 3 groups. NPC reduced totalcholesterol by 46.6% and CPC reduced it by 18.6%. NPC also significantly reduced low density lipoprotein (LDL)-cholesterol by 55.7%, while CPC reduced by 36.8%.high density lipoprotein (HDL)-cholesterol content was increased more with NPC by 16.5% than with CPC by 9.6%. Triacylglycerol content was also decreased significantly by 42.8% with NPC, while reduced by 22.5% with CPC. The present study indicated that NPC feeding reduced total andLDL-cholesterol and triacylglycerol contents and increased HDL-cholesterol content.
Effects of Chitosan on Plasma Lipids and Lipoproteins: A 4-Month Prospective Pilot Study
Chitosan can favorably modulate plasma lipids, but the available data are not conclusive. We evaluated the effect of chitosan on plasma lipids and lipoproteins in 28 patients with plasma Triglyceride levels >150 mg/dL (mean age: 63 ± 12 years), not taking other lipid-lowering agents. All patients received a chitosan derived from fungal mycelium (Xantonet, Bromatech, Italy) at a fixed dose of 125 mg/d in addition to their current medications for 4 months. Polyacrylamide gel electrophoresis was used to measure low-density lipoprotein (LDL) subclasses. After treatment, total cholesterol reduced by 8%, LDL cholesterol by 2%, and Triglycerides by 19%, with a concomitant 14% increase in high-density lipoprotein cholesterol. We also found a beneficial effect of chitosan on LDL subclasses, with a significant increase in LDL-2 particles (from 37 ± 8% to 47 ± 8%, P = .0001) and a decrease (although not significant) in atherogenic small, dense LDL. Whether these findings may affect cardiovascular risk remains to be established in future studies.
Cholesterol-lowering properties and safety of chitosan
Chitosan (CAS 9012-76-4) is derived by alkaline deacetylation from chitin, an abundant polymeric product of natural biosynthesis especially in crustaceans. It is available in a primary, unorganised structure, but also in a microcrystalline form. As a dietary supplement, chitosan has been claimed to control obesity and to lower serum cholesterol. A variety of chitosan products have been freely available worldwide in health stores and pharmacies. This review summarises the current knowledge about cholesterol-lowering and safety properties of chitosan and focuses its possible application for the treatment of hypercholesterolaemia. Chitosan behaves as a polycationic(+) cellulose-like fibrillar biopolymer that forms films with negatively charged surfaces. It is not specifically hydrolysed by digestive enzymes in man, but limited digestion of chitosan due to bacterial flora and to the unspecific enzymes might occur. Negatively charged molecules in stomach attach strongly to the positive charged tertiary amino group (-NH3+) of chitosan. Therefore, chitosan reduces fat absorption from gastrointestinal tract by binding with anionic carboxyl groups of fatty and bile acids, and it interferes with emulsification of neutral lipids (i.e., cholesterol, other sterols) by binding them with hydrophobic bonds. In short-term animal studies the safety of chitosan has been good. There are only few studies with chitosan in humans. In man, dietary chitosan has been reported to reduce serum total cholesterol levels by 5.8-42.6% and low-density lipoprotein levels by 15.1-35.1%. In short-term trials up to 12 weeks, no clinically significant symptoms have been observed with chitosan compared to placebo. Mild and transitory nausea and constipation have been reported in 2.6-5.4% of subjects. Although chitosan has been clinically well tolerated, it cannot be recommended to people allergic to crustaceans.
This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood Triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and Triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.
Cichorium intybus L. var. foliosum Hegi extract
Antioxidativeeffects of cichorium intybus root extract on LDL (low density lipoprotein) oxidation
The water extract of Cichorium intybus (WECI) showed a remarkable antioxidativeeffect onLDL, andInhibitoryeffects on the production of thiobarbituric acid reactive substance and the Degradation of fatty acids inLDL. Vitamin E and unsaturated fatty acids inLDL were protected by adding WECI from theeffects of metal catalyzedLDL oxidation. From the results obtained, we conclude thatLDL oxidation is inhibited in vitro by the addition of WECI, and thatLDL is protected by WECI from oxidative attack, as shown by agarose gel electrophoresis.
Effect of Cichorium intybus L. on fatty liver induced by oxytetracycline in albino rats.
Results: Fatty liver groups showed high significant increase in serum glucose, cholesterol, Triglycerides, LDL cholesterol, ALAT, ASAT, GGT, LDH, urea, creatinine and A/G ratio while total protein, albumin, globulin and HDL cholesterol were significantly decreased compared to control group. These biochemical changes were accompanied with histopathological alterations in fatty liver tissue. The treatment with chicory ameliorated most of the evaluated biochemical parameters and improved the induced degenerative histopathological changes. The pre-treatment with chicory before the induction of fatty liver gave some protection against factors that experimentally induced fatty liver.
Conclusion: Chicory as diet additive is recommend for fatty liver patients or those people who have hyperlipidemic family history.
Diabetes mellitus is associated with increased levels of inflammation and oxidative stress in patients. The aim of the present study was to test the hypothesis that aqueous extract of Cichorium intybus seeds (AECIS) would have add-on beneficial effect in type 2 diabetes mellitus (T2DM). In this double-blind randomized clinical study, 150 subjects were enrolled to assess the add-on efficacy and safety of AECIS in T2DM patients. The subjects were randomized (1:1) to the AECIS (n = 51) and placebo (n = 49) groups. The subjects in both groups continued to take prescribed doses of metformin. The standardization of AECIS was carried out by liquid chromatography–mass spectrometry and phytochemical analysis. The mean hemoglobin A1c (HbA1c) level in the AECIS and placebo groups at baseline was 8.6% and 8.5%, respectively. Mean values of HbA1c at the end of 12 weeks of intervention were 7.42% in the AECIS group (a reduction of 1.18% from baseline) and 8.4% in the placebo group (mean reduction of 0.1% from baseline). Besides, significant reduction in inflammation, oxidative stress, and hyperTriglyceridemia was seen in the AECIS group (p < .05). The study shows for the first time that AECIS supplementation ameliorates the disease progression and it is beneficial as a potential adjunct dietary supplement for the management of T2DM.
Cinnamomum Zeylanicum bark
Introduction
Atherosclerosis is one of the major causes of disability ofblood vessels which can result in development of many cardiovascular disorders. There is a strong association betweenAtherosclerosis and insulin resistance and dyslipidemia.
Aim
To study theAnti-atherosclerotic potential of C. zeylanicum bark extract in insulin resistance associatedAtherosclerosis and worsened Atherogenic Index (AI) associated with dyslipidemia, which are the predominant complications of steroid diabetes in Wistar rats.
Materials and Methods
A sum of 36 rats were categorized into five study groups and one plain control. In a 12 day study period, respective drug treatments were given every day throughout the study period whereas, dexamethasone dosage was started from day seven onwards. On day 12, fastingblood samples were collected and processed forlipid estimation and the determined values were also used to assess AI further. Animals were sacrificed under ether anaesthesia and the aorta was dissected away for its measurement and histopathological findings. One-way ANOVA was used to analyse the data and multiple comparison was done, interpreted based on Post-Hoc Scheffe test.
Results
high dose of dexamethasone (8 mg/kg/i.p) in Dexa Control (DC) group produced significant dyslipidemia, increased risk of atherogenicity (p<0.05) and caused severe thickening (78.5% compared to Plain Control (PC) of wall of aorta. Rosiglitazone (ROSI) (8 mg/kg and 16 mg/kg) and C. zelanicum (CZE) extract treatments (500 mg/kg and 250 mg/kg) significantly prevented dyslipidemia, well maintained AI compared to dexa control (p<0.05). However, both the CZE treatments protected the aorta fromAtherosclerosis (40.3% and 30.2% compared to DC) and significantly prevented the dyslipidemia and reduced the risk of atherogenicity compared to ROSI treatment (p<0.05). Although, the CZE did not show difference in significance in maintaining very low density lipoprotein when compared to ROSI (p>0.05). The atherosclerotic changes were completely absent in both the CZE treatments whereas, ROSI treatments did not prevented theAtherosclerosis of aorta completely as they showed moderate and mild atherosclerotic changes in the aorta.
Conclusion
The aqueous extract of C. zelanicum bark exhibited marked protection against dexamethasone inducedAtherosclerosis and also minimized the atherogenic risk in Wistar rats.
Purpose
According to the World Health Organization (WHO), approximately 150 million people worldwide have type 2 diabetes. It is a growing health concern. Common and cassia cinnamon have been reported to have anti-diabetic andlipid-lowering effects. The objective was to determine if the combination of common and cassia cinnamon (Cinnamomum verum and C. aromaticum) reduces fastingbloodglucose, insulin, glycosylated hemoglobin (HA1C), Triglyceride , totalcholesterol, HDLcholesterol andLDLcholesterol levels in people with type 2 diabetes.
Methods
Fifty (50) type 2 diabetic participants were randomized to receive either 140 mg of Cinnamonforce twice daily or placebo over 13 weeks. Physical and laboratory measurements were taken at baseline, 2 weeks, 4 weeks, 8 weeks and at the end of the trial, 13 weeks.
Results
There were no significant improvements in fastingglucose, insulin andlipid parameters between treatment and placebo groups. At endpoint, subjects in the treatment group were found to have a marginally non-significanthigher fastingbloodglucose level than subjects taking the placebo (p=0.085). There was a non-significant decrease in HA1c in the treatment group versus the placebo group (p=0.172). In secondary outcomes, significant differences in weight (p= 0.008), BMI (p= 0.001) and waist-to-hip ratio (p=0.020) were detected in the treatment versus placebo groups.
Conclusion
The combination of common and cassia cinnamon do not impact fastingglucose, insulin andlipid measurements. Through power calculations, there may be aneffect on HA1c, however, the sample size in this study was not sufficient to detect a trend, if any. Although secondary outcomes in this study, common and cassia cinnamon should be further investigated for weight loss.
Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits
The purpose of the present study was to investigate the lipid lowering effect of Cinnamomum zeylanicum (Cinnamon) in hyperlipidaemic albino rabbits. For this purpose, forty eight albino rabbits were randomly divided into eight equal groups; untreated control on normal routine feed, untreated control on butter and cholesterol, treated control on synthetic cholesterol lowering drug simvastatin (Tablet survive (R) 20 mg), three treated groups on three respective doses of C. zeylanicum bark powder and two treated groups on water and methanol extracts of C. zeylanicum bark powder. Butter ad lib and cholesterol powder 500 mg/kg body weight were used to induce experimental hyperlipidaemia in all groups except untreated control group. The results suggested that C. zeylanicum bark powder at the rate of 0.50 g/kg, 0.75 g/kg and methanol extract equivalent to 0.75 g/kg powder produced respective percent reductions in total lipids by 45, 49 and 64; Triglycerides by 38, 53 and 60; total cholesterol by 53, 64 and 69 and LDL-cholesterol by 50, 59 and 62. However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53. Nonetheless, C. zeylanicum bark powder at the level of 0.25g/kg and C. zeylanicum extract in water could not significantly reduce lipid profile indicators. Based on these studies, it can safely be said that C. zeylanicum bark powder methanol extract equivalent to 0.75g/kg bark powder and simvastatin (0.6 mg/kg b. wt.) were equieffective in treating hyperlipidaemia.
Clerodendrum minahassae
Leilem, which is known with the botanical name Clerodendrum minahassae, is a plant species commonly used as a component of almost all meat- and fish-based cuisine. In addition to enhancing the flavor and taste suited to the local people, leaves of leilem is also believed to possesshigh level of natural antioxidant. The leaves of this plant has also been used as traditional medicine to treat stomachache and lung diseases. Our previous study revealed that ethanol extract of leilem has beneficial antihyperlipidemic andAntiatheroscleroticeffects on the aorta of Wistar rats fed withhighlipid andcholesterol levels. The present study was aimed at investigating the phytochemical contents and antioxidant activity of ethanol extract of leilem leaves. Phytochemical screening was carried out using standard methods of precipitation and coloration reactions. In addition, the total phenolics and flavonoids were determined by using spectrophotometric methods. Finally, the leaf extract of leilem was assayed to evaluate its in vitro antioxidant properties using 1,1-Diphenyl picryl hydrazyl (DPPH) radical assay and ferricreducing antioxidant potential (FRAP) assay. The phytochemical screening of leilem leaves revealed the presence of alkaloids, saponins, flavonoids, steroids, and phenols, while terpenes and tannins were not detected. The extract of leilem leaves showed estimated phenolics and flavonoid content of 139.88 mg/g and 34.46 mg/g respectively. Concentration of leilem leave extract required for 50% inhibition of DPPH radical scavengingeffect (IC50) was recorded as 565.45 μg/mL. At 1 mg/mL concentration, the aqueous extract of leilem leaves showed ferricreducing power of 123.62 μmoles/mg in FRAP assay. These findings suggest that the ethanol extract of leilem has potential in vitro antioxidant activities. Overall, results obtained from this study support our previous finding that the extract of leilem leaves has beneficial antihyperlipidemic andAntiatheroscleroticeffects and can be used as an alternative to synthetic antioxidants.
Our previous study revealed that ethanol extract of leilem has beneficial antihyperlipidemic and antiatherosclerotic effects on the aorta of Wistar rats fed with high lipid and cholesterol levels. Extract of leilem leaves was able to decrease Triglyceride levels as well as increase HDL levels. Moreover, it also improved the aorta by reducing the number of foam cells and the thickness of the aortic wall. The purpose of this study was to investigate the phytochemical contents and antioxidant activity of ethanol extract of leilem leaves.
Codonopsis pilosula (Franch.)Nannf.root extract
effects of Codonopsis pilosula crude polysaccharides by hypoglycemic and modulating gut microbiome in ahigh-fatdiet and streptozotocin-induced mouse model of T2DM
The study explored the nature and structure of ultrasonically extracted Codonopsis pilosulae crude polysaccharides (CPCPs) and theeffects of CPCPs on hypoglycemiceffects and gut flora in ahighglucose andhigh-fat feeding and STZ-induced T2DM mice model. The results showed that the CPCPs consisted mainly of polysaccharides, uronic acids, proteins and SO42−. CPCPs consisted of β-type pyranose and exhibited porous, irregular fibrillation and aggregation, and inhibited the activity of α-amylase and α-glucosidase. 1 g/kg CPCPs reduced diabetic symptoms, including modulation of body weight andblood biochemistry levels, reducedblood sugar andlipids, liver, kidney, pancreas indices, oxidative damage and inflammatory factor levels in T2DM mice. For diabetic mice gut microbes, 1 g/kg CPCPs reduced the ratio of Firmicutes and Bacteroidetes; at the genus level and reduced Enterobacter abundance and increased Bacteroides abundance. These results suggested that CPCPs may beeffective supplements for preventing or treating of T2DM.
Protective Effect of Codonopsis lanceolata Root Extract Against Alcoholic Fatty Liver in the Rat
Alcohol intake remains the most important cause of fatty liver throughout the world. The current study was undertaken to determine whether dietary supplementation with Codonopsis lanceolata root water extract attenuates the development of alcoholic fatty liver in rats and to elucidate the molecular mechanism for such an effect. Male Sprague-Dawley rats were fed normal diet (ND), ethanol diet (ED) (36% of total energy from ethanol), or 0.5% C. lanceolata root extract-supplemented ethanol diet (ED+C) for 8 weeks. C. lanceolata root water extract supplemented to rats with chronic alcohol consumption ameliorated the ethanol-induced accumulations of hepatic cholesterol and Triglyceride. Chronic alcohol consumption up-regulated the hepatic expression of genes involved in inflammation, fatty acid synthesis, and cholesterol metabolism, including tumor necrosis factor α (TNFα), liver X receptor α (LXRα), sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase, acetyl-coenzyme A carboxylase α (ACC), stearoyl-coenzyme A desaturase 1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), and low-density lipoprotein receptor (LDLR). The ethanol-induced up-regulations of TNFα, LXRα, SREBP-1c, HMGR, and LDLR genes in the liver were reversed by feeding C. lanceolata root water extract for 8 weeks. Moreover, ethanol-induced decreases in the ratio of phospho-5′-AMP-activated protein kinase (AMPK) α/AMPKα and phospho-ACC/ACC protein levels in the liver were significantly restored (135% and 35% increases, respectively, P < .05) by supplementing them with C. lanceolata root water extract. In conclusion, C. lanceolata root water extract appears to be protective against alcoholic fatty liver through the regulation of SREBP-1c, LXRα, HMGR, and LDLR genes and by the phosphorylation of AMPKα and ACC, which are implicated in lipid metabolism.
A homogeneous polysaccharide coded as CPP−1 was extracted and purified from the root of Codonopsis pilosula (Franch.) Nannf. by water extraction, ethanol precipitation, and column chromatography. Its structure was analyzed by HPGPC-ELSD, HPLC, GC-MS, FT-IR, and NMR techniques. The results indicated that CPP−1 was composed of mannose (Man), glucose (Glc), galactose (Gal), and arabinose (Ara) at a molar ratio of 5.86 : 51.69 : 34.34 : 8.08. The methylation analysis revealed that the main glycosidic linkage types of CPP−1 were (1→)-linked-Glc residue, (1→3)-linked-Glc residues, (1→4)-linked-Gal residue, (1→2,3,4)-linked-Glc residue, (1→)-linked-Man residue, (1→3,4)-linked-Glc residue, and (1→)-linked-Ara residue. In vivo efficacy trial illustrated that CPP−1 supplements could alleviate HFD-induced mice obesity significantly, as well as improve obesity-induced disorders of glucose metabolism, alleviate insulin resistance, and improve the effects of lipid metabolism. The findings indicate that this polysaccharide has the potential for the treatment of obesity.
Coenzyme Q10
Context: Previous meta-analyses have suggested that theeffects of coenzyme Q10 (CoQ10) onlipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuatinglipid profiles in adults.
Objective: This study conducted a meta-analysis to determine theeffects of CoQ10 onlipid profiles and assess their dose-response relationships in adults.
Methods: Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The randomeffects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulatinglipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose-response relationships.
Results: Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced totalcholesterol (TC) (MD -5.53 mg/dL; 95% CI -8.40, -2.66; I2 = 70%), low-density lipoproteincholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 = 54%), and Triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04, -4.08; I2 = 65%) and increasedhigh-density lipoproteincholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose-response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01).
Conclusion: CoQ10 supplementation decreased the TC,LDL-C, and Triglyceride levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatesteffect on TC.
The Redox Status of Coenzyme Q10 in TotalLDL as an Indicator of In Vivo Oxidative Modification
Familial combined hyperlipidemia (FCH) is characterized by a familial occurrence of a multiple-type hyperlipidemia, associated with coronary risk. The latter may be related to increased levels of small, denseLDL particles that have been found to be more prone to oxidative modification. We isolated totalLDL as fresh as possible from 12 normolipidemic relatives with a buoyantLDL subfraction profile (group 1), 7 normolipidemic subjects with a denseLDL subfraction profile (group 2), and 16 hyperlipidemic FCH subjects with a denseLDL subfraction profile (group 3). In these nonobese and normotensive men, we studied the resistance of totalLDL against Cu2+-oxidation in vitro. In addition, we analyzed the α-tocopherol and the coenzyme Q10 contents ofLDL and determined their relation toLDL oxidizability.LDL isolated from group 3 subjects was more susceptible to oxidative modification thanLDL from group 1 subjects (lag time: 60.4±8.1 versus 70.4±11.4 minutes; P<.05). For the combined groups, the ratio of ubiquinol-10 to polyunsaturated fatty acids inLDL, together with the basal amount of dienes inLDL, were good predictors of the rate ofLDL oxidation (R2=.73, P=.0001). In groups 2 and 3, the redox status of coenzyme Q10 (ubiquinol-10/ubiquinone-10) and the ratio of ubiquinol-10 to α-tocopherol inLDL were reduced compared with group 1 (P<.05). The K-value, a measure of theLDL density, correlated with the the redox status (r=.37, P<.05). We conclude that in subjects with FCH totalLDL is more prone to oxidation, due to the predominance of denseLDL particles. In addition, the decreased redox status of coenzyme Q10 inLDL from subjects with a denseLDL subfraction profile suggests that theLDL in the circulation has already undergone some oxidation.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Results and discussion
Seven trials were included in the meta-analysis, involving 356 patients. Neither CoQ10 alone nor CoQ10 plus fenofibrate improved glycemic control. In addition, CoQ10, alone or in combination with fenofibrate, did not alter LDL-C, HDL-C and blood pressure. Triglycerides levels were significantly reduced with CoQ10 (mean difference −0·26 mmol/L, 95% CI −0·05 mmol/L to −0·47 mmol/L, P = 0·02) and CoQ10 plus fenofibrate (mean difference −0·72 mmol/L, 95% CI −0·32 mmol/L to −1·12 mmol/L, P = 0·0004). CoQ10 plus fenofibrate also effectively reduced total cholesterol (mean difference: −0·45 mmol/L, 95% CI −0·06 mmol/L to −0·84 mmol/L, P = 0·02).
What is new and conclusions
CoQ10 supplementation has no beneficial effects on glycemic control, lipid profile or blood pressure in patients with diabetes. However, it may reduce Triglycerides levels. Due to limited data availability, well-powered and well-designed randomized controlled trials are needed to clearly determine the effect of CoQ10 on metabolic profile in diabetes. Dosage effects should also be explored.
Results
All 101 subjects were included in the analysis. On the 12th week, compared to placebo, CoQ10 supplementation decreased systolic (P = .010) and diastolic pressure (P = .001) and increased serum total antioxidant capacity (TAC; P = .003). On the 24th week, compared to placebo, CoQ10 supplementation further lowered blood pressure and TAC, reduced Triglyceride (P = .020) and low-density lipoprotein cholesterol (P = .016), and increased ApoA-I (P < .001) while decreasing homeostasis model assessment of insulin resistance index (P = .009). Adjustment for change of physical activity and energy intake did not alter the effect of CoQ10 on the aforementioned parameters but led to significant decrease of non–high-density lipoprotein cholesterol in CoQ10 group compared to placebo (P = .031).
Conclusions
Twenty-four-week treatment of CoQ10 ameliorates multiple CVD risk factors. The versatility and safety of CoQ10 makes it a potential candidate for the primary prevention of CVD.
Problem statement: Hyperlipidemia is well known to play a main role in the development of atherosclerosis. It is characterized by abnormally elevated cholesterol, Triglyceride, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels in the blood. It has been recognized for many years that hypercholesterolemia is a major risk factor for cardiovascular diseases such as atherosclerosis, myocardial infraction, heart attacks and cerebrovascular diseases. In recent years, Coenzyme Q10 has gained considerable attention as a dietary supplement capable of influencing cellular bioenergetics and as a supplementary treatment for some chronic diseases. Approach: The present study was undertaken to evaluate whether Coenzyme Q10 supplementation would alter high cholesterol diet-induced hypercholesterolemic model in female rats. Sixty female albino rats of the Wistar strain weighing between 34.3 and 42.1 g were used. The experimental animals were divided into six groups. Rats of group 1 served as controls, fed with standard diet and had free access to water for three months. Rats of group 2 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months. Animals of group 3 were daily supplemented with 1 mL of corn oil containing 10 mg of cholesterol/rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 4 were daily supplemented with 1 mL of corn oil /rat for two months. The experimental rats of group 5 were daily supplemented with 1 mL of corn oil /rat for two months and daily supplemented with 1 mg Coenzyme Q10/rat at third month. Rats of group 6 were supplemented with 1 mg Coenzyme Q10/rat at third month. The body weight percentage changes were determined after second and third months in all experimental groups. Results: After 2 months, the maximum changes of body weight were noted in groups treated with high cholesterol diet and corn oil. After three months, the maximum percentage changes were observed in groups two and four and the minimum changes were noted in sixth group supplemented with only Coenzyme Q10 at last period. Serum Triglycerides, cholesterol, High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), Very Low Density Lipoprotein Cholesterol (VLDL-C), Atehrogenic Index (AI) and HDL Cholesterol (HDL-C) ratio were assessed at the end of experimental period. Significant increases in the levels of Triglycerides, cholesterol, LDL-C VLDL-C were noted in rats supplemented with high cholesterol diet, while the level of HDL-C was significantly reduced. Similar observations were noted in rats treated with high cholesterol diet plus Coenzyme Q10. Statistically, the treatment of Coenzyme Q10 in rats subjected to high cholesterol diet showed a decrease in the change levels of these parameters. Also, the Atehrogenic Index (AI) value was significantly elevated in rats supplemented with high cholesterol diet compared with control value. Administration of Coenzyme Q10 for a period of one month to rats supplemented with high cholesterol diet significantly decreased the percentage change of the Atehrogenic Index (IA) value. HDL-C ratio value was significantly decreased in rats supplemented with high cholesterol diet compared with control value. Treatment with Coenzyme Q10 for a period of last month significantly decreased the percentage change of the HDL-C ratio value in rats fed with high cholesterol diet. Conclusion: The present results suggested that Coenzyme Q10 possesses hypolipidemic effects in rats supplemented with high cholesterol diet. Thus, use of Coenzyme Q10 may be useful in the treatment of cardiovascular diseases in which atherosclerosis plays a major role.
Coptis chinensis Franch.root extract
Hypoglycemic andhypocholesterolemiceffects of Coptis chinensis franch inflorescence
Hypocholesterolemic and hypoglycemic activities of Coptis chinensis franch inflorescence (Coptis inflorescence) were studied using animal models.serum total andLDLcholesterol of rats fed adiet containing 1%cholesterol and 0.5% cholic acid increased, as compared with those of rats fed a normaldiet. The level of total andLDLcholesterol were reduced markedly in a dose dependent manner, in rats given Coptis inflorescence extract orally at doses of 0.25, 0.5 g/kg.day for 4 weeks. In diabetic rats induced by alloxan, Coptis inflorescence extract showed a significant (p < 0.05)blood sugarlowering activity at all experimented doses (0.125, 0.25 and 0.5 g/kg.day). Thehighest reduction ofblood sugar was about 58% when the rats were given Coptis inflorescence extract orally at a dose of 0.5 g/kg.day for 3 weeks. The 100 g dried water extract of Coptis inflorescence contained 8.11 g total alkaloid, 3.34 g berberin, 1.08 g palmatine and 0.66 g jatrorrhizine, which had long been identified as active compounds in Coptis chinensis franch root (Coptis root). Thus, the results suggest that Coptis inflorescence would beeffective in the prevention and management of coronary artery disease byloweringserumcholesterol andblood sugar.
Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters Fed High-Fat diet
Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high-fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), Triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up-regulated low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and down-regulated apical sodium-dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up-regulating LDLR and CYP7A1 mRNA and protein expression, down-regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia.
The effect of the MeOH extract of Coptidis Rhizoma on cell survival and adipogenesis in 3T3-L1 adipocytes is shown in Fig. 1A–C. The cytotoxicity of the MeOH extract obtained from Coptidis Rhizoma was measured by MTT assay. As shown in Fig. 1A, the MeOH extract of Coptidis Rhizoma exerted no cytotoxic effect at concentrations up to 200 μg/mL. The inhibitory effect of the MeOH extract obtained from Coptidis Rhizoma on Triglyceride contents in differentiated adipocytes was analyzed (Fig. 1B). As demonstrated in Fig. 1B, pretreat- ment with different concentrations of the MeOH extract (0, 12.5, 25, and 50 μg/mL) from Coptidis Rhizoma inhibited cellular Triglyceride accumulation in a dose dependent manner. Increased lipid accumulation during differentiation of preadipocytes into adipocytes is a typical phenomenon that occurs in 3T3-L1 cells and is used as a marker of differentiation. Lipid accumulation in cells was quantified by directly measuring Triglyceride levels. Triglycerides of fully differentiated adipocytes were stained with Oil-Red O staining solution (Fig. 1C). In the absence of the MeOH extract, fully differentiated cells had several lipid droplets as evidenced by the absorbance value of Oil-Red O eluted solution at 500 nm. The absorbance value of eluted dye was significantly decreased in the presence of the MeOH extract in a dose-dependent manner.
Cordycepin
The results suggested that levels of serum total cholesterol (TC), Triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) increased markedly in the two animal models by feeding high-fat diet. Meanwhile, cordycepin reduced levels of serum TC, TG, LDL-C, VLDL-C as well as LDL-C/HDL-C (high density lipoprotein cholesterol) and TC/HDL-C ratios. In concert with these effects, an increase in lipoprotein lipase (LPL) and hepatic lipase (HL) activity afforded by cordycepin was considered to contribute to the regulation on lipid profiles. Furthermore, no toxicity of cordycepin was observed by intragastric administration at the maximal tolerant dose in ICR mice for 14 days. The exact lipid-lowering effect of cordycepin needs further investigation.
Cordyceps polysaccharide
Blood was collected from each hamster using heparinized capillary tubes and centrifugated to obtain plasma. Total cholesterol (TC) and Triglyceride (TG) levels and LPL activity in the post-heparin plasma were assayed, and the lipid profiles of the lipoproteins were evaluated via the previous method
Costus spicatus (Jacq.) Sw.
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats
Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate theeffects of this species against the development ofAtherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenicdiet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days.serumlipidsoxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1β and 6, and markers of renal and liver function were measured. Renal function,blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. Results: Prolonged treatment with ESCS induces significanthypolipidemic and antioxidanteffects, that prevent endothelial dysfunction and modulated the local inflammatory process,reducing the evolution of the atherosclerotic disease. Conclusions: This study provides a scientific basis for the popular use of C. spicatus for the treatment ofAtherosclerosis.
The present study of antidiabetic effects of rhizome extracts of C. spicatus on STZ in diabetic rats was evaluated, important mechanism; underlying hyperglycemia in diabetes mellitus. Excess of glucose in blood leads diabetes. It reacts with haemoglobin and forms glycosylated. Therefore, the total haemoglobin level is decreased in STZ diabetic rats. Administration of C. spicatus ethanolic rhizome extract reversed the total haemoglobin levels in STZ diabetic rats. Our study we observed that haemoglobin level is lowered in diabetic treated rats. After twenty eight days treatment ethanolic rhizomes extract showed important reduction of blood glucose level. It showed effectively maintain blood glucose level in normal and STZ induced diabetic rats. Different group of animals were used; ethanolic extract of C. spicatus treated groups (200 and 300 mg/kg BW) another treated groups glibenclamide, used as standard, results in rats showed a significantly increased insulin level when compared with diabetagenic rats treated groups as well as in the group of glibenclamide.
In diabetic rats, the effects of hydrogen bonding, cyaniding-3-glucoside, and delphinidin-3-glucoside on the activity of α-amylase and α-glucosidase were compared using potential extraction powder (20). To defend the body against the harmful effects of reactive oxygen species (ROS), the antioxidant system functions as a complex network of enzymes and non-enzymatic molecules that work together (47). To evaluate the effects of hypoglycemia, etc., in diabetic rats, measurements of glucose, glutathione, Triglycerides, HDL, LDL, and other relevant biomarkers in their serum would be necessary (28, 40). Non- enzymatic glycation, also referred to as the Maillard reaction, is a process where sugar molecules bind to proteins, lipids, and nucleic acids without the involvement of enzymes. (14, 48). AGEs (Advanced Glycation Endproducts) are molecules that result from the binding of glucose to proteins or lipids in the body. It is believed that they contribute to the development of microvascular complications in diabetes, such as neuropathy, nephropathy, and retinopathy (30).
Crataegus pinnatifida Bge. var majorN.E.Br. fruit extract
Theeffects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Metabolic syndrome is described as a group of risk factors in which at least three unhealthy medical conditions, including obesity,highblood sugar, hypertension or dyslipidemia occur simultaneously in a patient. These conditions raise the risk for diabetes mellitus and cardiovascular diseases. Many recent studies have focused on herbal remedies and their pharmacologicaleffects on metabolic syndrome. Crataegus pinnatifida or Chinese hawthorn has been widely used in the treatment of hyperlipidemia and cardiovascular diseases. Its leaves, fruits and seeds have various active substances such as, flavonoids, triterpenic acids and sesquiterpenes, which through different mechanisms can be beneficial in metabolic syndrome. Flavonoids found in the leaves of hawthorn can significantly reduce atherosclerotic lesion areas, the fruit extracts contain two triterpenic acids (oleanolic acid and ursolic acid), that have the ability to inhibit the acyl-coA-cholesterol acyltransferase (ACAT) enzyme and as a result reduce very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL)cholesterol levels. Another example regards a sesquiterpene found in the seeds of C. pinnatifida, which exhibits the ability to inhibit platelet aggregation, thus showing antithrombotic activity. Various studies have shown that C. pinnatifida can have beneficialeffects on controlling and treatinghighblood sugar, dyslipidemia, obesity andAtherosclerosis. The aim of this review is tohighlight the interestingeffects of C. pinnatifida on metabolic syndrome.
Consumption of functional foods for managing plasmacholesterol level has gained acceptance globally. The hypocholesterolaemic and vascular protectiveeffects of the dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), were investigated in rats fed with normaldiet,highcholesteroldiet (HCD) or HCD plus Shan Zha 80% ethanolic extract treatment (30 or 100 mg/kg/day, p.o.) for 4 weeks. Shan Zha extract markedlyreversed the increased plasma totalcholesterol andhigh density lipoproteincholesterol induced by HCD with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function byreducinglipid content in the liver. The blunted endothelium-mediated aortic relaxation in HCD-fed rats was restored byhigh dosage of Shan Zha extract treatment. The current results showed that Shan Zha extract could provide itscholesterolloweringeffect by up-regulating hepatic CYP7A1 mRNA expression which leads to enhanced bile acid biosynthesis. It is postulated that the hypocholesterolaemiceffect is the primary beneficialeffect given by Shan Zha extract; it then leads to other secondary beneficialeffects such as vascular protective and hepatoprotective functions. Thus, Shan Zha extract could provide an overall improvement on the hepatic and vascular systems that may be important in relieving hypercholesterolaemia-related complications.
The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review
Insulin resistance is a common underlying factor in the formation of several diseases like obesity, dyslipidemia, hypertension, type 2 diabetes, and coronary diseases (31). Studies show that insulin resistance can be a contributing factor for the development of non-alcoholic fatty liver disease (NAFLD) (32) which consists of a spectrum of problems starting from the deposition of Triglyceride (TG) in the liver and then steatohepatitis and finally to fibrosis and cirrhosis (33).
In a recent 2015 study, the anti-obesity effects of a combination of C. pinnatifida leaf and Citrus unshia peel extracts (HTO48) were explored. In-vivo studies were performed on male Sprague Dawley rats. The rats were divided into two groups of chow diet group –and high fat diet group (HFD). Results showed that 0.2% and 0.6% concentrations of HTO48 (for 12 weeks) were able to reduce serum total cholesterol (TC) by 14.4% and 16.3 % and Triglyceride (TG) serum levels by 33.7 % and 31.9% in HFD-fed rats compared to the HFD control group. It was also shown that HTO48 was able to significantly reduce the expression of sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthase (FAS) genes, which are lipogenic genes that were higher in the HFD groups compared to the rats receiving a normal chow diet. Adipogenesis is a process in which preadipocytes mature into adipocytes by the enlargement of intracellular lipid droplets (a process involved in the formation of obesity) (42). In the study, the effects of different doses of HTO48 were examined on 3T3 -L1 preadipocytes by observing the expression of genes related to adipogenesis (PPAR Gama, aP2 and LPL mRNA). It was shown that HTO48 was able to significantly reduce lipid droplet formation and TG accumulation, thus inhibiting 3T3 -L1 preadipocytes differentiation into mature adipocytes. HTO48 was also able to reduce the expression of adipogenic transcription genes [peroxisome proliferator-activated receptor alpha (PPARg) and C/EBPa mRNA] and stimulate glycerol release (promoting lipolysis) in 3T3 -L1 adipocytes.
A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20–60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks , the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of Triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.
Crocetin
Objective:
Inhibition oflipidmetabolism in breast cancer has been suggested as aneffective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shownhypolipidemiceffect in diabetes andAtherosclerosis. Here, we investigated theeffect of Crt/Cro onlipid content in breast cancer.
Materials and Methods:
A multi-model approach involving in vivo, in vitro and in silico studies was applied. The 4T1-induced breast cancer in mice was used to investigate theeffect of Crt/Cro oncholesterol (Chl) and Triglyceride (TG) levels inserum and tumor tissues. The Chl/Triglyceride levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis.
Results:
Crt reduced bothserum (p=0.003) and tumor (p=0.011) Chl and Triglyceride (p=0.001) levels in mice. Cro reduced Triglyceride levels in tumor (p=0.014) andserum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and Triglyceride in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR withhigher affinity (ΔG0=-6.6 kcal/mol) than simvastatin (ΔG0 =-6.0 kcal/mol).
Conclusion:
Crt and Croeffectively decreased Chl/Triglyceride content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed ahigherhypolipidemic potential than Cro. In silico analysis indicated Crt binding in the HMGCR active site.
The pancreatic lipase inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum TG level in corn oil feeding-induced Triglyceridemic mice, as well as that of serum Triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Crocin
effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach
Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycatingeffect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, andlipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes inLDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations inLDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycatedLDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism betweenLDL and crocin. Molecular docking supports these results with ahighly negative binding energy of −10.3 kcal/mol, suggesting the formation of a stableLDL-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation ofLDL in people with such disorders.
The pancreatic lipaseInhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract asInhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase ofserum Triglyceride level in corn oil feeding-induced Triglyceride mic mice, as well as that ofserum Triglyceride and total andLDLcholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showedhypolipidemic activity in hyperlipidemic mice induced byhighcholesterol,high fat orhigh carbohydratediets for 5 weeks. The results suggest that thehypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Mechanism of hypolipidemic effect of crocin in rats: Crocin inhibits pancreatic lipase
The hypolipidemic mechanism of crocin, an active ingredient in Gardenia jasminoides Ellis and Crocus sativus L, was examined in rats. In diet-induced hyperlipidemic rats, a 10-day treatment with crocin significantly reduced serum Triglyceride, total cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol level in the daily dose range of 25 to 100 mg/kg. Results of the modified fat-loading method indicated that crocin inhibited the absorption of fat and cholesterol and this inhibition is closely related to the hydrolysis of fat. In addition, the modified fat-balance method demonstrated that crocin increased the fecal excretion of fat and cholesterol in rats, but had no influence on the elimination of bile acids. The results of the in situ loop method and enzyme assay indicated that crocin could not directly block the absorption of cholesterol from rat jejunum but could selectively inhibit the activity of pancreatic lipase as a competitive inhibitor. These findings suggest that crocin yielded its hypolipidemic effect by inhibiting pancreatic lipase, leading to the malabsorption of fat and cholesterol.
Cuphea carthagenensis
Abstract
Ethnopharmacological relevance
Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment ofAtherosclerosis and circulatory disorders, no study evaluating theseeffects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimentalAtherosclerosis model using New Zealand (NZ) rabbits undergoingcholesterol-richdiet (CRD).
Material and methods
Dyslipidemia and atherogenesis were induced by administration of standard commercialdiet increased of 1%cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRDdiet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks.serum levels of Triglyceride (TG), totalcholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined.
Results
CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase inlipid peroxidation and a reduction of hepatic glutathione andserum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC,LDL-C, VLDL-C levels and Triglycerides and promoted an increase in HDL-C levels in NZ rabbits. Theseeffects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment.
Conclusions
This study demonstrated that ES-CC reducesserumlipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-inducedAtherosclerosis.
Ethnopharmacological relevance
Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD).
Material and methods
Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100 mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of Triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined.
Results
CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and Triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment.
Conclusions
This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis.
Curcuma longa L. extract
It is generally accepted that free-radical inducedbloodlipid peroxidation and especially peroxidizedLDL play a central role in the pathogenesis ofAtherosclerosis and related cardiovascular disease. Moreover, recent researchhighlights the key contribution ofapolipoprotein B (apo B) to atherogenesis as the main inductor of one of its earlier steps, i.e. macrophage prolipheration. This has led us to investigate the apo B response to a veryeffective phenoliclipid-antioxidant, namely an hydroalcoholic extract of Curcuma longa, which according to our previous work does not show any toxiceffects and decreases the levels ofbloodlipid peroxides,oxidized lipoproteins and fibrinogen. The present study shows that a daily oral administration of the extract decreases significantly theLDL and apo B and increases the HDL and apo A of healthy subjects. This and recent data on the increased anti-atherogenic action of the physiological antioxidant tocopherol in the presence of phenolic co-antioxidants (which eliminate the tocopheroxyl radical), justifies planned clinical research to test the usefulness of the curcuma extract as a co-antioxidant complement to standard treatments to prevent or retardAtherosclerosis.
Background: Adipocytes accumulate triacylglycerol when excessive food consumption. Adipocyte dysfunction plays an important role in the obesity development. People with a body weight 40 % heavier than the average body weight population at risk of death two times greater than the average body weight. The use of anti-obesity drugs have many side effects, so it is necessary to find the anti-obesity drug with low toxicity. This ex vivo study was conducted to determine the activity of C. longa L. extract in inhibiting Triglycerides and cholesterol synthesis and lipid droplet formation on HepG2 cells compared to curcumin.
Methods: Anti-obesity activity includes reduced formation of lipid droplet in HepG2 cells can be observed using oil red O staining method. The measurement of Triglyceride level was performed according to Randox protocol using Randox TR 210 assay kit. Lipolytic activity by measuring cholesterol levels was performed based on Randox CH 200 kits.
Results: This study suggested that the extract of C. longa L. and curcumin have potential anti-obesity compounds. C. longa L. extract have higher activity in inhibiting Triglycerides and cholesterol synthesis compared to curcumin with inhibition activities 70.43% and 66.38% respectively in the highest concentration.
Conclusion: The C. longa extract posses the anti-adipogenesis potential on inhibiting the synthesis of Triglycerides and cholesterol and lipid droplet formation in HepG2 cell as anti-obesity parameters better than curcumin.
Metabolic syndrome (MS) involves people with the following risk factors: obesity, hypertension, high glucose level and hyperlipidemia. It can increase the risk of heart disease, stroke and type 2 diabetes mellitus. The prevalence of MS in the world’s adult population is about 20%–25%. Today, there is much care to use medicinal plants. Turmeric (Curcuma longa) as well as curcumin which is derived from the rhizome of the plant, has been shown beneficial effects on different components of MS. Thus, the purpose of this manuscript was to introduce different in vitro, in vivo and human studies regarding the effect of turmeric and its constituent on MS. Moreover, different mechanisms of action by which this plant overcomes MS have been introduced. Based on studies, turmeric and its bioactive component, curcumin, due to their anti-inflammatory and antioxidant properties, have antidiabetic effects through increasing insulin release, antihyperlipidemic effects by increasing fatty acid uptake, anti-obesity effects by decreasing lipogenesis, and antihypertensive effects by increasing nitric oxide. According to several in vivo, in vitro and human studies, it can be concluded that turmeric or curcumin has important values as a complementary therapy in MS. However, more clinical trials should be done to confirm these effects.
Curcumin
Atherosclerosis is a major cause of cardiovascular disease caused byhighcholesterol. Reduced intestinalcholesterolabsorption has been shown to exert strongcholesterol-lowering and antiatherogeniceffects. Previously, we reported that curcumin reducedcholesterolabsorption inhigh-fatdiet–fed hamster by downregulating the intestinal expression of Niemann-Pick C1-like 1. Here, we tested the hypothesis that supplementation with curcumin can also reduce intestinalcholesterolabsorption inhigh-fatdiet–fedapolipoprotein E knockout (ApoE−/−) mice and preventAtherosclerosis development. ApoE−/− mice were fed ahigh-fatdiet supplemented with or without curcumin (0.1% w/w) for 16 weeks. Aortic sinus sections revealed that curcumin supplementation reduced the extent of atherosclerotic lesions by 45%. Curcumin treatment also reducedcholesterol accumulation in the aortas by 56% and lowered plasma totalcholesterol and low-density lipoproteincholesterol levels. Moreover, the antiatherogenic andcholesterol-lowering effects of curcumin coincided with a significant decrease in intestinalcholesterolabsorption. It was reduced by nearly 51%, and the decreasedcholesterolabsorption was modulated by inhibiting the intestinal expression of Niemann-Pick C1-like 1, predominantly in the duodenal and jejunal segments of the small intestine. These findings support the hypothesis that curcumin supplementation reduces intestinalcholesterolabsorption and preventsAtherosclerosis inhigh-fatdiet–fed ApoE−/− mice. Curcumin affords a potent antiatherogenic action by inhibiting intestinalcholesterolabsorption in the mouse.
Regulation ofPCSK9 by nutraceuticals
PCSK9, a criticalInhibitor ofLDLR, is up-regulated by both HNF1α and SREBP-2 transcription factors. Besides
PCSK9, SREBP-2 up-regulatesLDLR gene. Nutraceuticals, including curcumin and berberine, can decrease plasma
LDL-C levels through elevation of the hepaticLDLR via inhibiting HNF1α which is a specific transcription factor
forPCSK9 gene. Statins increase the expression of bothPCSK9 andLDLR through the activation of SREBP-2,
resulting inPCSK9-mediated attenuation of theireffects
Background
dietary phytosterols (PS) are well-known hypocholesterolaemic agents. Curcumin elicits hypolipidaemic and anti-inflammatoryeffects in preclinical studies, however, consistent findings in humans are lacking.
Objective
Concurrent PS and curcumin supplementation may exhibit enhanced hypocholesterolaemic and anti-inflammatoryeffects to optimise cardio-protection. The objective of this trial was to investigate theeffects ofdietary intervention with PS with or without curcumin onbloodlipids (primary outcome) in hypercholesterolaemic individuals.
Methods
A double-blinded, randomised, placebo-controlled, 2 × 2 factorial trial was conducted in hypercholesterolaemic individuals. Participants received either placebo (PL, no phytosterols or curcumin), phytosterols (PS, 2 g/d), curcumin (CC, 200 mg/d) or a combination of PS and curcumin (PS-CC, 2 g/d–200 mg/d respectively) for four weeks. Primary outcomes included fasting totalcholesterol (TC),LDL-cholesterol, HDL-cholesterol, Triglycerides (TG), TC-to-HDL-C ratio (TC:HDL-C). Secondary outcomes included anthropometrics and fastingbloodglucose concentrations.
Results
Seventy participants with a mean (±SEM) fasting TC concentration of 6.57 ± 0.13 mmol/L completed the study (PL, n = 18; PS, n = 17; CC, n = 18; PS-CC, n = 17). PS and PS-CC supplementation significantly lowered TC,LDL-cholesterol and TC:HDL-C post-intervention (p < 0.05). Reductions from baseline in the PS group were 4.8% and 8.1% for TC andLDL-cholesterol respectively (p < 0.05). CC exhibited non-significant reduction (2.3% and 2.6%) in TC andLDL-C respectively, however, the PS-CC resulted in a greater reduction in TC (11.0%) andLDL-cholesterol (14.4%) than either of the treatments alone (p < 0.0001). The reduction in the PS-CC treatment was significantly greater compared to those for CC (p < 0.05) or PL (p < 0.01) alone. Plasma HDL-cholesterol and Triglyceride concentrations remained unchanged across all groups. No adverse sideeffects were reported.
Conclusions
The addition of curcumin to phytosterol therapy provides a complementarycholesterol-loweringeffect that is larger than phytosterol therapy alone. Implications of these findings include the development of a single functional food containing both the active ingredients for enhancedlipid-lowering and compliance in hypercholesterolaemic individuals.
Background
Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD).
Methods
A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and Triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect.
Results
The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = −0.340, 95% confidence interval [CI]: −0.530 to −0.150, P < 0.0001) and TG (SMD = −0.214, 95% CI: −0.369 to −0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = −0.934, 95% CI: −1.289 to −0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = −0.584, 95% CI: −0.980 to −0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies.
Conclusions
Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.
Human studies of curcumin extract on lipid-lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty-five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high-density lipoprotein cholesterol (HDL-C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The Triglyceride-lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL-C effect in female patients, both of which result in a decrease of T-Chol/HDL-C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid-lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol-related parameters, especially in metabolic syndrome patients.
Scope: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism.
Methods and results: LDLR(-/-) mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, Triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment.
Conclusion: Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.
Molecular mechanisms of hypolipidemic effects of curcumin
Recent evidence suggests potential benefits from phytochemicals and micronutrients in reducing the elevated oxidative and lipid-mediated stress associated with inflammation, obesity, and atherosclerosis. These compounds may either directly scavenge reactive oxygen or nitrogen species or they may modulate the activity of signal transduction enzymes leading to changes in the expression of antioxidant genes. Alternatively, they may reduce plasma lipid levels by modulating lipid metabolic genes in tissues and thus reduce indirectly lipid-mediated oxidative and endoplasmic reticulum stress through their hypolipidemic effect. Here we review the proposed molecular mechanisms by which curcumin, a polyphenol present in the rhizomes of turmeric (Curcuma longa) spice, influences oxidative and lipid-mediated stress in the vascular system. At the molecular level, mounting experimental evidence suggests that curcumin may act chemically as scavenger of free radicals and/or influences signal transduction (e.g., Akt, AMPK) and modulates the activity of specific transcription factors (e.g., FOXO1/3a, NRF2, SREBP1/2, CREB, CREBH, PPARγ, and LXRα) that regulate the expression of genes involved in free radicals scavenging (e.g., catalase, MnSOD, and heme oxygenase-1) and lipid homeostasis (e.g., aP2/FABP4, CD36, HMG-CoA reductase, and carnitine palmitoyltransferase-I (CPT-1)). At the cellular level, curcumin may induce a mild oxidative and lipid-metabolic stress leading to an adaptive cellular stress response by hormetic stimulation of these cellular antioxidant defense systems and lipid metabolic enzymes. The resulting lower oxidative and lipid-mediated stress may not only explain the beneficial effects of curcumin on inflammation, cardiovascular, and neurodegenerative disease, but may also contribute to the increase in maximum life-span observed in animal models.
Curcumin is an herbal polyphenol extensively investigated for antioxidant, anti-inflammatory, and hypolipidaemic properties. In the present review, the efficacy of curcumin for improving a plasma lipid profile has been evaluated and compared with statins, a well-known class of medicines for treating hypercholesterolemia and hyperlipidaemia. Curcumin is presumably most effective in reducing Triglyceride (TG), while statins are most efficient in lowering low-density lipoproteins-cholesterol (LDL-C). Additionally, various molecular and metabolic mediators of cholesterol and plasma lipid homeostasis are discussed in relation to how they are modulated by curcumin or statins. Overall, curcumin influences the same mediators of plasma lipid alteration as statins do. Almost all the pathways through which cholesterol trafficking takes place are affected by these agents. These include gastrointestinal absorption of dietary cholesterol, hepatocellular removal of plasma cholesterol, the mediators of reverse cholesterol transport, and removal of cholesterol from peripheral tissues. Moreover, the reactive oxygen species (ROS) scavenging potential of curcumin limits the risk of lipid peroxidation that triggers inflammatory responses causing cardiovascular diseases (CVD) and atherosclerosis. Taken together, curcumin could be used as a safe and well-tolerated adjunct to statins to control hyperlipidaemia more effectively than statins alone.
Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat–fed hamsters
This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, Triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and Triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid β-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat–fed hamsters.
Cyclocarya paliurus
Results
Different Cyclocarya paliurus polar extracts, especially ChE reduced the levels of serum total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and hepatic TC and TG, enhanced the level of serum high-density lipoprotein cholesterol (HDL-C), restored hepatic and renal function indices and histomorphology. HMG-CoA reductase activity and mRNA expression were decreased, while CYP7A1 activity and mRNA expression as well as the level of fecal and hepatic bile acid were increased by ChE. LC–MS analysis of ChE revealed the presence of six main triterpenoids, which might be responsible for its antihyperlipidemic bioactivity.
Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague–Dawley rats
Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague–Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)–1) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, Triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and Triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction.
Cymodocea nodosa
This study aims to evaluate for the first time theeffects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo tohigh fatdiet (HFD)-rats on body weight,lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats inserum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads tolipid regulation shown by the decrease of totalcholesterol (T-Ch), Triglycerides (TG) and low density lipoproteincholesterol (LDL-C) and an increase inhigh density lipoproteincholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters inblood.
This study aims to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on lipase activity in vitro and in vivo to high fat diet (HFD)-rats on body weight, lipid profile and liver-kidney functions. The administration of CNSP decreases the body weight and inhibits lipase activity of obese rats in serum and intestine as compared with untreated HDF-rats. This decrease in lipase activity leads to lipid regulation shown by the decrease of total cholesterol (T-Ch), Triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) and an increase in high density lipoprotein cholesterol (HDL-C) levels in HFD-rats. Additionally, CNSP administration to HFD-rats induces anti-oxidant activity observed by the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels and protects liver-kidney functions proven by a decrease in the levels of toxicity parameters in blood.
This new study aimed to evaluate for the first time the effect of Cymodocea nodosa extract (CNE) on α-amylase activity, hyperglycemia and diabetes complications in the alloxan-induced diabetic rats. The in vitro evaluation and oral administration of CNE to surviving diabetic rats inhibited key enzyme related to hyperglycemia as α-amylase, helped to protect the β cells of the rats from death and damage confirmed by oral glucose test tolerance (OGTT), which leads to decrease in blood glucose level by 49% as compared to untreated diabetic rats. The CNE also decreased the Triglyceride, low density lipoprotein (LDL) cholesterol and total cholesterol rates in the plasma of diabetic rats by 46%, 35%, and 21%, respectively, and increased the high density lipoprotein (HDL) cholesterol level by 36%, which helped maintain the homeostasis of blood lipid. When compared to those of the untreated diabetic rats, the superoxide dismutase, catalase, and glutathione peroxidase levels in the pancreas, liver and kidney of the rats treated with this supplement were also enhanced significantly. Moreover, a significant decrease was observed in the lipid peroxidation level in the tested organs of diabetic rats after CNE administration. This positive effect of CNE was confirmed by histological study. Overall, the findings presented in this study demonstrate that CNE has both a promising potential with a valuable hypoglycemic and hypolipidemic functions.
Cynara scolymus L.leaves extract
hypolipidemic and antiatherogeniceffects of Cynara scolymus incholesterol-fed rats
Cynara scolymus L., Asteraceae, are traditionally used to treat dyspepsia. This study evaluated thehypolipidemic and antiatherogeniceffects of an aqueous extract prepared from the leaves of C. scolymus in rat’s model. hypercholesterolemic rats (1%cholesterol and 0.5% cholic acid for 15 days) were treated (0.5 ml/200 g) with extract of C. scolymus (150, 300, or 600 mg/kg p.o.; n = 6) or simvastatin (4 mg/kg p.o.; n = 6) once per day for 30 days along with hypercaloricdiet. A control group (C) was given water (0.5 ml/200 g; n = 6). Ahigh-cholesteroldiet was maintained throughout the treatment period. Rats treated with extract of C. scolymus (150, 300, or 600 mg/kg) and simvastatin showed significant decreases inserum levels of totalcholesterol (−46.9%, −51.9%, −44%, and −41.9%, respectively) and low-density lipoprotein-cholesterol (LDL-C; −52.1%, −54.8%, −51.9%, and −46.7%, respectively), compared with group C (p < 0.005). Biochemical analyses revealed significant decrease in the concentration of IL-1, IL-6, TNF-α, IFN-γ, C-reactive protein,oxidized-LDL, and antioxidized-LDL in rats treated with extract of C. scolymus (150, 300, or 600 mg/kg). There were no differences inserum ALT enzyme activity between the groups. Our results suggest thathypolipidemic and antiatherogeniceffects could be related with the presence of polar substances present in aqueous extract of C. scolymus.
Cynara scolymus (artichoke) and its efficacy in management of obesity
Obesity, the most prevalent metabolic disorder is associated with elevated body fat mass and body mass index. Cynara scolymus L. is famous for its hepatoprotective properties, also it seems to have good potency as anti-obese agent. In this review article, the potency of C. scolymus as anti-obese agent has been evaluated. The evidences based information were extracted from accessible international electronic databases (PubMed, Springer, Science Direct, Wiley and Google), and books (Persian or English), by key word of Cynara scolymus and artichoke plus obesity or the mechanism of anti-obese drugs. C. scolymus inhibits the digestive enzymes such as pancreas lipase, α-amylase, α-glucosidase, increases the bile secretion, inhibits of inflammation and ROS, improves liver function, gut microbiota, enhances lipolysis and lipid metabolism, and reduces blood glucose in preclinical and clinical studies. Designing large multi-center clinical trials on C. scolymus and evaluating its effects on weight loss in comparison with famous drug such as orlistate could be the subject of future studies.
Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, Triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.
The aim of this study was to assess the effect of artichoke (Cynara scolymus) leaf aqueous extract (ALE) on streptozotocin (STZ)-induced diabetic rats. ALE (200 and 400 mg/kg body weight) was administered to STZ-induced diabetic rats and fasting blood glucose, total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), atherogenic index, lipid peroxidation (LPO), red blood cell (RBC) superoxide dismutase (SOD) activity and plasma antioxidant capacity were measured. The oral administration of ALE for 21 days significantly reduced TC, TG, LDL-C, VLDL-C and hyperglycemia in treated diabetic rats as compared to diabetic control group. ALE also markedly ameliorated the level of plasma malondialdehyde (MDA) and increased plasma antioxidant capacity of treated diabetic group. The results clearly indicate the beneficial reducing effects of ALE on serum TC, TG, LDL-C, VLDL-C, glucose levels and plasma MDA level in STZ-treated rats.
Investigation of the Effect of Artichoke (Cynara Scolymus L.) on Characteristics of the Fatty Liver
On the other hand, lowering blood sugar, Triglyceride, and cholesterol levels showed the positive effects of this plant in reducing and improving liver function and treatment of hyperlipidemia [35]. Studies have shown that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. They have also indicated that this plant reduces lipids and lipoproteins by interfering with the biosynthesis of cholesterol and also affects the production and secretion of bile in the liver. It seems that the existence of flavonoid compounds in this plant is responsible for its effects, especially in improving liver’s function [40, 41].
Most of medications do not decrease TG levels, however, our results showed that C. dactylon not only reduces the lipid levels but also lowers the plasma level of TG.
Cynarin
Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or Triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.
Cynodon dactylon extract
Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study,Anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normaldiet, sham group received ahighcholesteroldiet (HCD; 1.50%cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including totalcholesterol (TC), Triglyceride (TG), low-density lipoproteincholesterol (LDL-C) andhigh-density lipoproteincholesterol (HDL-C) were assessed in theblood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changedlipid profile bylowering of TC, Triglyceride andLDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.
Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.
A Review of the Pharmacological and Nutraceutical Properties of Cynodon dactylon
Simultaneous administration of C dactylon extract caused a significant decrease in serum TC, LDL-c, and VLDL-c, suggesting a beneficial modulatory influence on cholesterol metabolism and turnover. The reduction in the ratio of TC:HDL-c observed in the extract-treated rats might be a consequence of a higher proportion of HDL-c, which could be due to increased reverse cholesterol transport from peripheral organs to the liver.33, 34 Elevated serum TG is considered an independent risk factor for CVD.35 TG accumulation caused by dietary cholesterol may contribute to the reduction of fatty acid beta-oxidation and the preference of cholesterol ester to afflux to LDL during the onset of biosynthesis and secretion of LDL.36, 37 A significant decline in the serum TG concentration observed in extract-treated rats supports the cardiovascular protective influence. The mechanism by which C dactylon extract lowered the serum TG concentration could be either by decreasing VLDL synthesis, by channeling VLDL through pathways other than to LDL, or an increase in lipoprotein lipase activity.
Antihyperlipedemic activity of Cynodon dactylon extract in high-cholesterol diet fed Wistar rats
The aim of the present study was to investigate the potential role of an ethanolic extract of the entire plant of Cynodon dactylon in lowering the plasma lipid parameters in rats fed a high cholesterol diet. Wistar albino rats were randomly divided into four groups of six and for 45 days were administered either: 0.5 ml water (negative controls); 30 mg cholesterol (hypercholesterolemic animals); C dactylon extract at 400 mg/kg body weight (positive control); or the same doses of both cholesterol and the extract (test animals). The effects of C dactylon on the lipid profile were assessed by measuring the plasma concentrations of total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and very low-density lipoprotein cholesterol (VLDL-c). Administration of cholesterol showed significant elevation (p < 0.001) of TC, LDL-c, VLDL-c, and TG concentrations, and of the TC:HDL-c ratio (p < 0.05). Concurrent administration of C dactylon extract caused a significant decrease (p < 0.001) in the concentrations of serum TC, LDL, HDL, VLDL TGs when compared with cholesterol fed control rats. The TC:HDL-c ratio was also declined significantly (p < 0.001). These results suggest lipid-lowering effects of C dactylon, which serves as a new potential natural product for preventing hyperlipidemia.
d-Allulose
d-Allulose, a C-3 epimer of d-fructose, is a rare sugar reported to be a non-caloric sweetener having several health beneficialeffects including anti-hyperglycemia and anti-obesity. However, the impact ofdietary d-allulose oncholesterolmetabolism remains unclear. Therefore, we studied theeffects of d-allulose on thecholesterolmetabolism of Golden Syrian hamsters, an animal model with alipidmetabolism similar to that of humans. Hamsters received either normaldiet (ND) orhigh-fatdiet (HFD) with or without 3% d-allulose for 4 or 8 weeks. While there were no significant differences in totalserumcholesterol levels between the groups, d-allulose significantly increased HDL-cholesterol levels in ND-fed hamsters and decreasedLDL-cholesterol levels in HFD-fed hamsters, causing an overall decrease in theLDL/HDL ratio. Furthermore,dietary d-allulose decreasedserum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in bothdiets. In conclusion, d-allulose may favorably modulatecholesterolmetabolism byreducingPCSK9 in hamsters.
d-Glucaric acid
The beneficial properties of different vitamins, minerals, and other micronutrients have been studied for quite some time. But only recently has the potential usefulness of d-glucaric acid and its derivatives in disease prevention been demonstrated. d-Glucaric acid is an end product of the d-glucuronic acid pathway in mammals. Itsdietary sources include different fruits and vegetables. In the present study, d-glucaric acid content in various fruits and vegetables was found to range from about 0.1 g/kg in grapes and lettuce to about 3.5 g/kg in apples and broccoli. It was also shown that purifieddiets containing calcium d-glucarate or potassium hydrogen d-glucarate markedly loweredserum levels ofcholesterol in female Sprague-Dawley rats. The d-glucarates reduced totalserumcholesterol in rats by up to 14% (P<0.05) and loweredLDL-cholesterol by up to 35% (P<0.05), but had noeffect on HDLcholesterol. These results provide a starting point for further studies of the mechanism by which d-glucaric acid salts lowerserumcholesterol.
Dendropanax morbifera
Antiobesity andcholesterol–lowering effects of Dendropanax morbifera Water Extracts in Mouse 3T3-L1 Cells
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, includingglucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they containhigh levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemiceffects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5–500 μg/mL in 24–72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells byreducing intracellular Triglyceride levels andglucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesityeffects in mouse 3T3-L1 cells. Because few studies have demonstratedcholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5–500 μg/mL in 24–72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular Triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
D. morbifera reduces bad cholesterol and Triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice.
The purpose of this study was to determine the effects of dried Dendropanax morbifera leaf extracts on lipid profiles of mice fed a high-fat and -cholesterol diet (HFCD). ICR mice were divided into six groups based on mice fed AIN-93G diet (Normal), HFCD (Control), HFCD+100 mg/kg/d of D. morbifera leaf aqueous extract (DA-100), HFCD+200 mg/kg/d of D. morbifera leaf aqueous extract (DA-200), HFCD+100 mg/kg/d of D. morbifera leaf ethanol extract (DE-100), or HFCD+200 mg/kg/d of D. morbifera leaf ethanol extract (DE-200) for 7 weeks. The final body weights of mice fed D. morbifera extracts were all lower than those of the control group. Mice treated with D. morbifera extracts showed significantly reduced plasma and hepatic Triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol levels, along with increased plasma high-density lipoprotein cholesterol level. Fecal TG level was higher in DE-100 and DE-200 groups and TC level was significantly higher in the DA-200 and DE-200 groups. Relative liver weight, spleen weight, and testicle fat weight in mice treated with D. morbifera were reduced compared to the control group. Plasma insulin, aspartate transaminase, and alanine transaminase levels of experimental groups were also lower than those of the control group. All mice treated with D. morbifera extracts had lower malondialdehyde (MDA) content and higher superoxide dismutase (SOD) activity than the control group. Particularly MDA levels of the DA-200 and DE-200 groups and SOD levels of the DE-200 group were identical to levels of the normal group. These results suggest that D. morbifera extracts have lipid improvement effects in mice fed a HFCD.
Dioscorea zingiberensis
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Dioscoreaceae (Dioscorea nipponica Makino)
Naturally OccurringPCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Diosgenin
The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review
Hyperlipidemia is a pathological disorder of lipid metabolism that has various causes. The clinical manifestations of hyperlipidemia include increased serum cholesterol, Triglycerides, and low-density lipoprotein cholesterol (LDL-C), and decreased serum high-density lipoprotein cholesterol (HDL-C). Imbalance of LDL-C and HDL-C can increase the risk of cardiovascular (CV) events, including myocardial infarction and stroke.1 Data released by the American Heart Association in 2018 showed that CV disease (CVD) is the most lethal disease worldwide.2 According to the 2010 global burden of disease study, 15.6 million people died of CVD, accounting for 29.6% of all deaths.3 Hyperlipidemia has a long disease course, and many underlying causes, reflecting its complex etiology.4 Dyslipidemia is a significant risk factor for coronary artery disease and stroke; hence, prevention and appropriate management of dyslipidemia can markedly lower the related morbidity and mortality.5
Diospyros kaki Thunb. extracts
cholesterol-loweringeffect of astringent persimmon fruits (Diospyros kaki Thunb.) extracts
This study aimed to investigate theeffects of ethanol extract of astringent persimmon on antioxidant activity,cholesterol, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and mRNA expression ofcholesterolmetabolism-related genes in human hepatoma cell line (HepG2 cells). In the results, DPPH and ABTS radical scavenging activity showed that the different types cultivars of astringent persimmon was similar to Vitamin C as positive control. However, there are not significant differences among samples. In addition, our results showed thatcholesterol amounts and HMG-CoA reductase activity were inhibited by astringent persimmon in HepG2 cells. Further, treatment with astringent persimmon upregulated the expression ofLDL receptor and SREBP-2, and also increased the level of HDL-associated ABCA1. Taken together, our results indicate that astringent persimmon regulatecholesterol accumulation by inhibiting the oxidative stress and controlling the levels ofLDL & HDLassociated gene.
This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. Methods: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. Results: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic Triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol 7α-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. Conclusion: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
In this study, immature persimmon (Diospyros kaki Thunb.) ethanol extract was administered to an obese animal model fed a high-fat diet to measure weight change, adipose tissue weight, serum lipid level, and expression level of adipose-related genes to evaluate its efficacy. Administration of D. kaki ethanol extract (DKE) (100 and 500 mg/kg/d) decreased the body weight gain, adipose tissue weight, and serum Triglyceride levels in mice fed a high-fat diet. Furthermore, it improved the leptin and adiponectin levels in the blood as well as gene expression in the liver. It also inhibited the expression of sterol regulatory element-binding protein-1c, inhibiting the production of Triglyceride biosynthetic enzyme fatty acid synthesis and acetyl-CoA carboxylase, and decreased the expressions of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding proteins that induce adipocyte differentiation. Therefore, these data suggest that DKE exerts beneficial effects on high-fat diet-induced obesity by modulating lipid metabolism in mice fed a high-fat diet.
This study aimed to investigate the potential of freeze-dried persimmon powder (Diospyros kaki Thumb.) to protect against dyslipidemia induced by a high-fat/cholesterol diet (HFD) in a rat model. Methods: Fifty Wistar rats were randomly divided into five groups: normal control (NC), high-fat/cholesterol control (HC), tannin in HFD (HT, 1% of diet), immature persimmon in HFD (HI, 7% of diet), and mature persimmon in HFD (HM, 7% of diet). Tannin was used as a positive control. Biochemical, molecular, and histopathological changes were observed in the blood and liver. Results: We confirmed that a high fat/cholesterol diet successfully induced dyslipidemia, which was characterized by significantly altered lipid profiles in the plasma and liver. However, oxidized low-density lipoprotein levels, histopathological damage in the liver, and hepatic Triglyceride levels were significantly reduced in all HT, HI, and HM groups compared to those in the HF group. In contrast, plasma apolipoprotein B level was significantly reduced only in the HT and HM groups, whereas reduction of the LDL-C level was detected only in the HI group. Although HF-induced sterol regulatory element-binding protein (SREBP) gene expression was significantly reduced in all treated groups, downstream gene expression levels varied among the different groups; significant reduction of fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl-CoA (HMGCR) gene expression was detected only in the HI group, whereas cholesterol 7α-hydroxylase (CYP7A1) gene expression was significantly elevated only in the HM group. Conclusion: Taken together, the data suggest that protection of LDL oxidation and hepatic lipogenesis might be, at least partly, attributed to tannin in persimmons. However, the identified mechanisms varied up to the maturation stage of persimmon. In the case of immature persimmon, modulation of FAS and HMGCR gene expression was prominent, whereas in the case of mature persimmon, modulation of CYP7A1 gene expression was prominent.
Persimmon (Diospyros kaki) fruit: hidden phytochemicals and health claims
These beneficial effects may be due to the properties of its phenolic compounds (1.15 g / 100 g) and high fiber (63.48 g / 100 g) content (Innami et al., 1998[53]; Gorinstein et al., 1999[38]). In another study, Lee et al. (2006[77]) supplementation powdered whole persimmon leaf (5 %) and observed that supplementation results in lowering of blood cholesterol and Triglyceride, while increased ratio of HDL-C/total-C was also observed. In another study, Matsumoto et al. (2006[86]) supplemented diet with young persimmon fruit (10 %) that reslted in similar results i.e. lowering of total & LDL cholesterol and Triglyceride.
Docosahexaenoic Acid
Epidemiological and genetic studies suggest that elevated Triglyceride (TG)-rich lipoprotein levels in the circulation increase the risk of cardiovascular disease. Prescription formulations of omega-3 fatty acids (OM3FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma TG levels and are approved for the treatment of patients with severe hyperTriglyceridemia. Many preclinical studies have investigated the TG-lowering mechanisms of action of OM3FAs, but less is known from clinical studies.
EGb 761
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
A 12-week intervention with KRG was conducted in patients with impaired fasting glucose, impaired glucose tolerance, or newly diagnosed with T2DM. Subjects were randomized in a double-blind, placebo-controlled trial. The trial results showed that 12 weeks of intervention with KRG supplementation (5 g/day) led to normalization of whole blood and serum glucose levels as well as serum insulin and CRP concentrations (Bang et al., 2014). Administration of Panax Ginseng extract (PGE) for 8 weeks (6 g/day) decreased serum Triglycerides and total cholesterol and LDL levels, while increasing HDL levels. These results were attributed to PGE potent antioxidant effects (Kim and Park, 2003). In accordance, the effects of a low-dose (3 g/day) and a high-dose (6 g/day) of KRG supplementation for 8 weeks on antioxidant enzymes and oxidative stress markers in humans were assessed in a randomized, double-blind, placebo-controlled trial. Increased GSH-Px, SOD, and CAT activities were found in the high-dose group as compared to the placebo group. Plasma oxidized-LDL levels and DNA tail length and tail moment were significantly decreased in both high and low dose groups but increased in the placebo group. This led to the conclusion that supplementation with KRG upregulates antioxidant enzymes activities and consequently attenuates lymphocyte DNA damage
Elaeocarpus Ganitrus
ANTIOXIDANT AND lipid lowering effectS OF ELAEOCARPUS GANITRUS INcholesterol FED RABBITS
Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluateAntiatherosclerotic /lipidlowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) incholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits.lipid profile inserum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels ofserum totalcholesterol, Triglycerides , phospholipids,LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratioimproved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease inlipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
ANTIOXIDANT AND LIPID LOWERING EFFECTS OF ELAEOCARPUS GANITRUS IN CHOLESTEROL FED RABBITS
Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluate antiatherosclerotic /lipid lowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) in cholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits. Lipid profile in serum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels of serum total cholesterol, Triglycerides, phospholipids, LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratio improved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease in lipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
The present study was designed to investigate the antiatherosclerotic and antioxidant activity of 70% ethanolic crude extract of Elaeocarpus ganitrus seed in cholesterol fed rabbits. The E. ganitrus extract was administered at a dose level of 250 and 500 mg/kg/day (p.o) for 120 days to cholesterol fed rabbits. Lipid profile in serum and tissue biochemistry as well as antioxidant parameters in heart were determined. The histological change in coronary artery was examined. Statistical analysis was carried out by using One way ANOVA followed by Tukey’s multiple comparison tests using Graphpad PRISM software (version 5). Rabbits fed with cholesterol and E. ganitrus extract concurrently showed significant (P ≤ 0.01, ≤ 0.001) decrease in the levels of serum total cholesterol, Triglycerides, phospholipids, LDL, VLDL and atherogenic index along with a considerable improvement in HDL ratio in a dose dependant manner. Further, a significant reduction was also recorded in the levels of total cholesterol, Triglycerides; phospholipids in heart of plant extract administered group animals. Lipid peroxidation levels decreases significanlty as well as marked elevation in Glutathione, Catalase and SOD levels were observed in treated group rabbits. Histopathological analysis revealed significant increase in lumen size of coronary arteries when E. ganitrus extract supplemented concurrently to cholesterol fed animals. Our study exhibited that the phytoconstituents like phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the E. ganitrus ethanolic extract may be attributed to the significant antiatherosclerotic as well as antioxidant activity, signifying the potential protective role in coronary artery disease.
Emodin
Naturally OccurringPCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Rheum palmatum Linn has been widely applied in the clinical treatment of diabetes mellitus. It has been found that emodin as the major bioactive component of R. palmatum L exhibits the competency to activate peroxisomal proliferator-activated receptor-gamma (PPARgamma) in vitro. So the aim of this study was to evaluate the anti-diabetic effects of emodin through the activation of PPARgamma on high-fat diet-fed and low dose of streptozotocin (STZ)-induced diabetic mice. The diabetic mice were intraperitoneally injected with emodin for three weeks. No changes of food consumption and the body weight in emodin-treated mice were monitored daily during the entire experiment. At the end of experiment, the levels of blood glucose, Triglyceride and total cholesterol in serum were significantly decreased after emodin treatment. However, serum high-density lipoprotein cholesterol (HDLc) concentration was significantly elevated. The glucose tolerance and insulin sensitivity in emodin-treated group were significantly improved. Furthermore, the results of quantitative RT-PCR analysis showed that emodin significantly elevated the mRNA expression level of PPARgamma and regulated the mRNA expressions of LPL, FAT/CD36, resistin and FABPs (ap2) in liver and adipocyte tissues. No effects on the mRNA expressions of PPARalpha and PPARalpha-target genes were observed. Taken together, the results suggested that the activation of PPARgamma and the modulation of metabolism-related genes were likely involved in the anti-diabetic effects of emodin.
Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of Triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of Triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation.
The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of emodin on high-fat diet (HFD)-induced obese rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed HFD for two weeks, Wistar rats were dosed orally with emodin (40 and 80 mg kg−1) or pioglitazone (20 mg kg−1), once daily for eight weeks. Emodin (80 mg kg−1 per day) displayed similar characteristics to pioglitazone (20 mg kg−1 per day) in reducing body weight gain, plasma lipid levels as well as coronary artery risk index and atherogenic index of HFD-fed rats. Emodin also caused dose related reductions in the hepatic Triglyceride and cholesterol contents and lowered hepatic lipid droplets accumulation in HFD-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in hepatocytes of HFD-fed rats. Our findings suggest emodin could attenuate lipid accumulation by decreasing lipogenesis and increasing mitochondrial fatty acid β-oxidation mediated by activation of the AMPK signaling pathway.
Emodin Ameliorates Ethanol-Induced Fatty Liver Injury in Mice
The liver plays a central role in ethanol (EtOH) metabolism, and oxidative stress is implicated in alcohol-mediated liver injury. The present study aimed to investigate the role of emodin in EtOH-induced fatty liver injury. Liver histology, biochemistry and gene-expression studies were performed. Mice fed with an EtOH-containing diet exhibited severe macrovesicular steatosis and higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. However, emodin ameliorated liver steatosis and lowered ALT and AST. Emodin also decreased hepatic Triglyceride in mice fed with EtOH. In addition, emodin attenuates Oil Red O staining in alcoholic fatty liver in mice. Hepatic cytochrome P450 2E1 protein levels were upregulated in EtOH-fed mice, but downregulated in emodin-treated mice. In addition, emodin decreased hepatic oxidative stress. Furthermore, emodin significantly reduced liver α-smooth muscle actin and collagen type I, whereas it increased the mRNA levels of PPAR-γ. Taken together, emodin plays protective roles in alcohol-mediated liver steatosis.
EPA (Eicosapentaenoic Acid)
Eicosapentaenoic Acid (Epa) – Uses, Side Effects, and More
EPA prevents the blood from clotting easily, reduces Triglyceride levels in the blood, and has effects that might reduce pain and swelling.
EPA is a US FDA-approved prescription drug for reducing Triglyceride levels. As a supplement, people most commonly use EPA for heart disease, preventing heart attack, and depression. It is also used for chemotherapy-related side effects, diabetes, recovery after surgery, and many other purposes, but there is no good scientific evidence to support many of these other uses.
Don’t confuse EPA with similar fatty acids, such as alpha-linolenic acid and DHA. See the separate listings for algal oil, alpha-linolenic acid, DHA, fish oil, and krill oil.
Epigallocatechin gallate (EGCG)
effect of EGCG onlipidabsorption and plasmalipid levels in rats
Catechins, compounds derived from green tea, have been shown to reduce plasmacholesterol levels and the rate ofcholesterolabsorption. We investigated the dose response and the mechanism of action of epigallocatechin gallate (EGCG) on these parameters in rats. Wistar rats were fed adiethigh incholesterol and fat containing either none, 0.25% (0.2 g/day/kg BW), 0.5% (0.4 g/day/kg/BW) or 1.0% (0.7 g/day/kg BW) of EGCG. After 4 weeks of treatment, totalcholesterol and low density lipoprotein plasma levels were significantly reduced in the group fed 1% EGCG when compared to the no treatment group. Plasma Triglycerides andhigh-density lipoprotein levels did not change significantly. Following a single oral application of a liquid test-meal, intestinalcholesterolabsorption in Wistar rats was 79.3% in the control group. In the group treated with 0.1 g/kg BW EGCG intestinalcholesterolabsorption decreased to 73.7% and in the group treated with 0.5 g/kg BW of EGCG intestinalcholesterolabsorption fell significantly to 62.7% (P = 0.005). Total fatabsorption was very efficient in the control group (99.5% of the applied dose) and decreased significantly but moderately in the group treated with thehighest doses of EGCG (0.75, 1 g/kg BW). In an in-vitro biliary micelle model, the addition of 55 microM to 1300 microM EGCG not only decreasedcholesterol solubility dose-dependently in these micelles but also altered the size of the mixed lecithin/taurocholate/cholesterol micelles as demonstrated by light scattering. This study provides evidence suggesting that thecholesterol-loweringeffect of green tea is mainly elicited by EGCG, one of the most abundant catechins contained in green tea. It is suggested that one of the underlying mechanisms by which EGCG affectslipidmetabolism is by interfering with the micellar solubilization ofcholesterol in the digestive tract, which then in turn decreasedcholesterolabsorption.
The (−)-gallocatechin gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins, as a result of sterilization. The present study aims to examine the effects of GCG-rich tea catechins on hyperlipidemic rats and the mechanisms associated with regulating cholesterol metabolism in the liver. By performing heat epimerization of (−)-epigallocatechin gallate (EGCG), we manufactured a mixture of catechins that had a GCG content of approximately 50% (w/w). In sucrose-rich diet-induced hyperlipidemic rats, the GCG-rich tea catechins exhibited strong activity in reducing plasma cholesterol and Triglyceride concentrations. Furthermore, the hepatic cholesterol and Triglyceride concentrations that had increased as a result of the sucrose-rich diet were reduced due to GCG-rich tea catechins consumption. In order to investigate the hyperlipidemic mechanism of GCG-rich tea catechins, we examined the hepatic expressions of LDL receptor and HMG-CoA reductase in hyperlipidemic rats. We further evaluated the action of purified GCG on LDL receptor activity, which is a key contributor to the regulation of cholesterol concentrations. We found that purified GCG increased LDL receptor protein level and activity to a greater extent than EGCG. In conclusion, our study indicates that GCG-rich tea catechins in tea beverages may be effective in preventing hyperlipidemia by lowering plasma and hepatic cholesterol concentrations.
Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma Triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are Triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.
Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma Triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are Triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.
Eritadenine (Lentinus edodes)
Cardiovascular diseases are among the main causes of death in our society and there is a strong correlation between enhancedbloodcholesterol levels and the development of such diseases. The popular edible fungus, shiitake mushroom (Lentinus edodes), has been shown to produce abloodcholesterollowering compound designated eritadenine, and thehypocholesterolemic action of this compound has been quite extensively examined in rats. Eritadenine is suggested to accelerate the removal ofbloodcholesterol either by stimulating tissue uptake or by inhibiting tissue release; there are no indications of this compound inhibiting the biosynthesis ofcholesterol. If shiitake mushrooms are to be used as a source for a potentialcholesterolreducing product, it is of great importance to determine the content of eritadenine in the mushrooms as accurately as possible. Hence, in paper I methanol extraction was used to recover as much as possible of thehypocholesterolemic agent from the fungal cells. In order to analyse the target compound, a reliable and reproducible HPLC method for separation, identification and quantification of eritadenine was developed. The amounts of eritadenine in fruit bodies of four commercially cultivated shiitake mushrooms were determined, and the mushrooms under investigation exhibited up to ten times higher levels of eritadenine (3.17-6.33 mg/g dry mushrooms) than previously reported. Not only the fruit bodies of shiitake, but also its mycelia contain eritadenine. Growing fruit bodies of shiitake is a fairly demanding and time consuming process. Hence, in search for a source of eritadenine, submerged (liquid) cultivation of shiitake mycelia could be an alternative.
The hypocholesterolemic action of eritadenine in the rat
The hypolipidemic properties of eritadenine, an adenine derivative isolated from the Japanese mushroom Lentinus edodes, were investigated in rats with an emphasis on the effect on plasma cholesterol.
Eritadenine lowered all the plasma lipid levels (cholesterol, Triglyceride and phospholipid) and it was more than 10 times as active as clofibrate when administered in the diet. Large oral doses of eritadenine produced a hypocholesterolemic effect 3 hours after administration. Plasma free cholesterol was more affected than esterified cholesterol. Parenteral routes of administration did not seem to be as effective as the oral route. Dietary hypercholesterolemia was also suppressed by eritadenine. The acute Triton-induced hyperlipidemia was slightly suppressed by eritadenine, but proportionally less than in the normal rat. Although adenosine showed no effect on the hypocholesterolemic action of eritadenine, a twenty-fold excess of adenine may have interfered with the action of eritadenine.
Synthesis and hypocholesterolemic activities of eritadenine derivatives
Hypercholesterolemia is now considered a major risk factor in the development of premature atherosclerosis. Several classes of hypolipidemic agents are now available for the control of hypercholesterolemia. These include the HMG-CoA reductase inhibitors [1] which inhibit cholesterol biosynthesis, the second generation fibric acid derivatives [2] which interfere with fatty acid synthesis and stimulates hepatic fatty acid oxidation, thus reducing the amount of fatty acid available to the liver for Triglyceride synthesis, and the bile acid sequestrants [3] which interrupt the enterohepatic circulation of bile acids. The other types of hypocholesterolemic agents have also been developed. For example, the selective estrogen receptor modulators [4] which change lipid metabolism [5] and the potent inhibitors of acyl-CoAcholesterol acyltransferase [6], [7], [8], [9], [10] which inhibit cholesterol esterification.
Eucommia ulmoides Oliver extract Chlorogenic acid
Biological Values of Acupuncture and Chinese Herbal Medicine: Impact on the Life Science
Intracellularglucose andlipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism.glucose andlipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in the humandiet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation toglucose andlipidmetabolism, have beenhighlighted. This review addresses current studies investigating the roles of CGA inglucose andlipidmetabolism.
Hypercholesterolemia is a major risk factor for the development of cardiovascular disease and nonalcoholic fatty liver disease. Natural compounds have been proved to be useful inloweringserumcholesterol to slow down the progression of cardiovascular disease and nonalcoholic fatty liver disease. In the present study, thehypocholesterolemic and hepatoprotectiveeffects of thedietary consumption of chlorogenic acid were investigated by monitoring plasmalipid profile (totalcholesterol, Triglycerides ,high-density lipoprotein and low-density lipoprotein) in Sprague-Dawley rats fed with a normaldiet, ahigh-cholesteroldiet or ahigh-cholesteroldiet supplemented with chlorogenic acid (1 or 10 mg/kg/day p.o.) for 28 days. Chlorogenic acid markedly altered the increased plasma totalcholesterol and low-density lipoprotein but decreasedhigh-density lipoprotein induced by a hypercholesterolemicdiet with a dose-dependent improvement on both atherogenic index and cardiac risk factor.lipid depositions in liver were attenuated significantly in hypercholesterolemic animals supplemented with chlorogenic acid. It is postulated thathypocholesterolemiceffect is the primary beneficialeffect given by chlorogenic acid, which leads to other secondary beneficialeffects such as atheroscleroprotective, cardioprotective and hepatoprotective functions. Thehypocholesterolemic functions of chlorogenic acid are probably due to the increase in fatty acids unitization in liver via theup-regulation of peroxisome proliferation-activated receptor α mRNA.
Chlorogenic acid as a natural hydroxycinnamic acid has protectiveeffect for liver. Endotoxin induced metabolic disorder, such aslipid dysregulation and hyperlipidemia. In this study, we investigated theeffect of chlorogenic acid in rats with chronic endotoxin infusion. The Sprague-Dawley rats withlipid metabolic disorder (LD group) were intraperitoneally injected endotoxin. And the rats of chlorogenic acid-LD group were daily received chlorogenic acid by intragastric administration. In chlorogenic acid-LD group, the area of visceral adipocyte was decreased and liver injury wasameliorated, as compared to LD group. In chlorogenic acid-LD group,serum Triglycerides , free fatty acids, hepatic Triglycerides andcholesterol were decreased, the proportion of C20:1, C24:1 and C18:3n-6, Δ9-18 and Δ6-desaturase activity index in the liver were decreased, and the proportion of C18:3n-3 acid was increased, compared to the LD group. Moreover, levels of phosphorylated AMP-activated protein kinase, carnitine palmitoyltransferase-I, and fatty acid β-oxidation were increased in chlorogenic acid-LD group compared to LD rats, whereas levels of fatty acid synthase and acetyl-CoA carboxylase were decreased. These findings demonstrate that chlorogenic acideffectively improves hepaticlipid dysregulation in rats by regulating fatty acidmetabolism enzymes, stimulating AMP-activated protein kinase activation, and modulating levels of hepatic fatty acids.
Anti-obesity compounds in green leaves of Eucommia ulmoides
The anti-hypertensive effect of Eucommia leaves has been confirmed clinically,1(a), 1(b) and the study of their anti-obesity properties has advanced.2 However, the compounds involved in their anti-obesity effect have not been fully elucidated. In this Letter, we examined the anti-obesity effect of Eucommia green leaf extract (EGLE) divided into five fractions with high porous polystyrene gel and of the compounds isolated, geniposidic acid, asperuloside and chlorogenic acid, respectively. A metabolic syndrome-like clinical model in mice was generated by feeding a 40% high-fat diet to examine the anti-obesity effects of chronic administration of test substance. After 4 weeks, body weight, white adipose tissue weight, plasma Triglyceride levels and total cholesterol levels in the model mice were significantly inhibited by the 30% MeOH fraction (containing much higher levels of asperuloside than the other fractions), and these effects were similar to those of EGLE. Chronic administration of isolated asperuloside in Eucommia leaves suppressed increases in model mouse body weight, white adipose tissue weight, plasma Triglyceride levels and free fatty acids levels. These results suggest that asperuloside in Eucommia leaves has important anti-obesity effects.
Facilitative effects of Eucommia ulmoides on fatty acid oxidation in hypertriglyceridaemic rats
BACKGROUND: Tea made from Eucommia ulmoides leaves is widely consumed as a health food, since recent studies have revealed various pharmacological effects of the tea, e.g. a hypotriglyceridaemic effect. This study was conducted to elucidate the mechanisms underlying the plasma Triglyceride-lowering effect of E. ulmoides leaves.
RESULTS: Rats were divided into four groups: a normal group, a group fed a high-fat/high-fructose diet (untreated group) and two groups fed a high-fat/high-fructose diet and E. ulmoides tea (4 or 20 g L−1 extract, treated groups). Plasma Triglyceride concentrations were reduced in treated groups in a dose-dependent manner compared with the untreated group. DNA microarray analysis revealed that genes involved in hepatic α-, β- and ω-oxidation, mainly related to the peroxisome proliferator-activated receptor α and δ signalling pathway, were up-regulated in the treated group. High-performance liquid chromatography analysis showed that E. ulmoides leaves contain three phytochemicals that make up 60 mg g−1 of the material and are likely to be the active components.
CONCLUSION: This study indicates that the promotion of fatty acid oxidation, probably by the action of phytochemicals, participates in the ameliorative effect of E. ulmoides leaves on hypertriglyceridaemia. These findings provide the scientific evidence for the functionality of E. ulmoides.
Numerous pharmacological studies have shown that E. ulmoides leaves have unique advantages in the treatment of metabolic diseases (Hosoo et al., 2017; Hao et al., 2016; Jin et al., 2010; Lee et al., 2018). To date, more than 110 compounds have been isolated from the leaves of E. ulmoides. They include flavonoids, lignans, phenolics, iridoids, steroids, terpenes, fatty acids, and volatile oils. Phenolics, flavonoids and iridoids are the major components of E. ulmoides leaves and can regulate NAFLD (Pisonero-Vaquero et al., 2015). Kobayashi. et al. showed that E. ulmoides leaf extract can decrease the serum Triglyceride (TG) level of rats fed a high-fructose/high-fat diet by regulating the oxidation of fatty acids in the PPARα and PPARδ signaling pathways (Kobayashi et al., 2012). However, the active site and mechanism of E. ulmoides leaves for lowering blood lipids remain unclear.
Health-Promoting Properties of Eucommia ulmoides: A Review
Eucommia ulmoides (EU) (also known as “Du Zhong” in Chinese language) is a plant containing various kinds of chemical constituents such as lignans, iridoids, phenolics, steroids, flavonoids, and other compounds. These constituents of EU possess various medicinal properties and have been used in Chinese Traditional Medicine (TCM) as a folk drink and functional food for several thousand years. EU has several pharmacological properties such as antioxidant, anti-inflammatory, antiallergic, antimicrobial, anticancer, antiaging, cardioprotective, and neuroprotective properties. Hence, it has been widely used solely or in combination with other compounds to treat cardiovascular and cerebrovascular diseases, sexual dysfunction, cancer, metabolic syndrome, and neurological diseases. This review paper summarizes the various active ingredients contained in EU and their health-promoting properties, thus serving as a reference material for the application of EU.
Eugenia jambolana
The aim of the present study was to investigate theAntiatheroscleroticeffect of active principle (FIIc) isolated from aqueous fruit pulp extract of Eugenia jambolana. Crude aqueous extract of E. jambolana was subjected to purification using chromatographic techniques which yielded purified active compound (FIIc). Purity of FIIc was tested by HPLC. Phytochemical investigation of FIIc by NMR, IR, and UV spectra showed that the purified compound is -hydroxy succinamic acid. The streptozotocin- (STZ-) induced diabetic rats were fed atherosclerotic (Ath)diet containing 1.5 mL olive oil containing 8 mg (3, 20,000 IU) vitamin and 40 mgcholesterol for 5 consecutive days. The STZ-induced diabetic rats receiving Athdiet were orally administered FIIc at doses of 10, 15, and 20 mg/kg, and results were compared with reference drug, that is, glibenclamide (600 g/mg) and healthy control. 30-day treatment with FIIc resulted in significant ( ) improvement inbloodglucose,serumlipid profile,apolipoproteins (Apo and apo ), and endothelial dysfunction parameters. Histomorphological studies also confirmed biochemical findings. Our results showed that FIIc has protectiveeffect on hyperglycemia-inducedAtherosclerosis.
ANTIDYSLIPIDEMIC EFFECT OF EUGENIA JAMBOLANA EXTRACT ON HIGH FAT DIET INDUCED DYSLIPIDEMIA IN RATS
Antidyslipidemic activity of extract of Eugenia jambolana (EJ, Jamun fruit) in adult Charles Foster rats of both sexes was studied and compared with that of Atorvastatin (Atorva). 4 groups were made [Gp 1- Control group (no drug), only high fat diet (HFD); Gp 2- HFD +EJ (evaluation of role of EJ in the prevention of dyslipidemia); Gps 3 & 4-only HFD]. This was the phase of disease production, lasting for 7 weeks, in which we also evaluated the preventive role of EJ. Thereafter, therapy phase started, which lasted for 90 days [Gp 1-Control group (no drug). Only HFD; Gp 3- HFD+ Atorva; Gp 4- HFD+EJ]. Parameters tested were TC (total cholesterol), TG (Triglycerides), LDL (low density lipoproteins) and HDL (high density lipoproteins). During the prevention/ disease production phase, EJ brought an improvement in TC level as compared to control group, which was statistically not significant; but improvements in TG, LDL & HDL levels were significant. Moreover, in the therapy phase, EJ brought significant improvement in all the parameters. It means to say, EJ takes some time in the initiation of a significant response- as we know that natural products take some time for the onset of their therapeutic effects. During therapy phase, Atorva was slightly more effective than EJ. Therefore, Eugenia jambolana, as a low-cost herbal therapy, offers an inexpensive, safe & effective measure to combat major public health problems viz dyslipidemia/ Coronary Artery Disease/ Atherosclerosis.
The hypoglycemic and hypolipidemic effects of flavonoid rich extract obtained from seeds of Eugenia jambolana (EJ) was analyzed in streptozotocin induced diabetic rats. Hypoglycemic activity was assessed by reduction in fasting blood glucose (FBG) and peak blood glucose level within 60 min of glucose tolerance test (GTT) in mild and severe diabetic (MD and SD respectively) rats. Different biochemical parameters like glycogen biosynthesis, glucose homeostatic enzyme (glucose-6-phosphatase, hexokinase) activities demonstrated significant (p < 0.05) improvement as compared to diabetic counter parts. Further, the flavonoids also stimulated 16% increase in insulin release in vitro from pancreatic islets. The hypolipidemic action after this extract supplementation was confirmed by significant (p < 0.05) decrease in the levels of LDL (27% MD, 29% SD), Triglycerides (about 35% MD, 37% SD) and increase in HDL (21% MD, 34% SD) over untreated diabetic rats. The above mentioned action of this plant extract was found to be through dual up regulation of both the peroxisome proliferators-activated receptors (PPARα and PPARγ) up to about 3–4 folds (over control) and their capacity to differentiate 3T3-L1 preadipocytes. The present data suggests that the flavonoid rich extract from EJ plant has both hypoglycemic and hypolipidemic effects which can help the cure and management of diabetes.
Eugenol (Syzygium aromaticum)
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Hypercholesterolemia is a dominant risk factor for atherosclerosis and cardiovascular diseases. In the present study, the putative antihypercholesterolemic and antioxidative properties of an ethanolic extract of Piper betle and of its active constituent, eugenol, were evaluated in experimental hypercholesterolemia induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg b.wt) in Wistar rats. Saline-treated hypercholesterolemic rats revealed significantly higher mean blood/serum levels of glucose, total cholesterol, Triglycerides, low density and very low density lipoprotein cholesterol, and of serum hepatic marker enzymes; in addition, significantly lower mean serum levels of high density lipoprotein cholesterol and significantly lower mean activities of enzymatic antioxidants and nonenzymatic antioxidants were noted in hepatic tissue samples from saline-treated hypercholesterolemic rats, compared to controls. However, in hypercholesterolemic rats receiving the Piper betle extract (500 mg/kg b.wt) or eugenol (5 mg/kg b.wt) for seven days orally, all these parameters were significantly better than those in saline-treated hypercholesterolemic rats. The hypercholesterolemia-ameliorating effect was better defined in eugenol-treated than in Piper betle extract-treated rats, being as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt). These results suggest that eugenol, an active constituent of the Piper betle extract, possesses antihypercholesterolemic and other activities in experimental hypercholesterolemic Wistar rats.
Euphorbia prostrate
A Database of Anti-Diabetic and Anti-Cancer Plant Species from the Family Euphorbiaceae
In alloxan-induced (150mg/Kg) serum biochemical parameters were were investigated in whole plant (methanolic extract) of Euphorbia prostrata (EP) (250 and 500 mg/Kg/day per oral for 14 days). The typical anti-diabetic medicine was glibenclamide (5 mg/kg/day per oral for 14 days). When compared to the control group alloxan-induced diabetics had higher fasting blood glucose, cholesterol and Triglyceride levels. Euphorbia prostrate extract (at dosages of 250 and 500 mg/kg) had an anti-diabetic levels significantly. In comparison to the 250 mg/Kg dose of Euphorbia prostrate, the 500 mg/Kg dose yielded more significant (P< 0.05) outcomes. At the end of the effect, lowering fasting blood glucose research, the levels of serum cholesterol and and Triglycerides were also reduced [22].
extruded Amaranth (Amaranthus caudatus L.)
Hypercholesterolemic rabbits, obtained by a specialdiet, were divided in three groups, and each group was fed a differentdiet for 21 days. Thediets were: extruded amaranthdiet (EAD),diet with amaranth oil (AOD) and a controldiet. Growth rates of rabbits were similar in all groups. After being fed the experimentaldiets, totalcholesterol andLDL-C concentrations were lower in rabbits fed the EAD than in those fed the AOD or the controldiet. Triglycerides and VLDL-C concentrations were approximately 50% lower in rabbits fed the EAD and the AOD than in rabbits fed the controldiet. No significant differences were found among HDL-C concentrations of the three groups. These results demonstrate that the consumption of extruded amaranth reducesLDL and totalcholesterol levels and may be another option to prevent coronary heart diseases.
Coronary artery disease (CAD), which is a multi-factorial disease frequently, causes morbidity and mortality in human beings. Scientists now believe that there is a good link between the inflammatory process and coronary atherosclerosis. A study was conducted to find out the anti- atherosclerosis effect of Amaranthus caudatus L. on rabbits, and was compared with lovastatin. Twenty five male New Zealand rabbits were randomly grouped into five and each were fed for 60 days with a standard diet, standard diet and cholesterol, standard diet and A. caudatus extract (150 mg/kg daily), standard diet and A. caudatus extract (150 mg/kg daily) with cholesterol, and standard diet with lovastatin (10 mg/kg) and cholesterol. At the 30th and 60th day of experiment, the biochemical factors were measured and the fatty streak formation was evaluated at the 60th day. Rabbits fed with high cholesterol diet and A. caudatus extract significantly decreased the cholesterol, LDL-C, Triglyceride, oxidized LDL (Ox-LDL), apo-lipoprotein B (apoB), CRP, atherogenic index (AI) and HDL-C and apo-lipoprotein A (apoA) increased. Lesion severity, in extract recipient group, significantly decreased. A. caudatus extract decreased the most important risk factors (the serum lipoproteins, apoB and Ox-LDL) of cardiovascular diseases and inflammatory factors prevented atherosclerosis and was more effective than lovastatin.
Fargesin
Background and aims
Fargesin mainly functions in the improvement oflipidmetabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affectsAtherosclerosis by regulatinglipidmetabolism and inflammatory response.
Methods and results
ApoE−/− mice were fed ahigh-fatdiet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage. Oil Red O, HE and Masson staining were performed to assess atherosclerostic plaques in apoE−/− mice. [3H] labeledcholesterol was used to detectcholesterolefflux andreversecholesteroltransport (RCT) efficiency. Enzymatic methods were performed to analyze plasmalipid profile in apoE−/− mice. Immunohistochemistry was used to analyze macrophage infiltration. THP-1-derived macrophages were incubated with fargesin or not. Both Western blot and qRT-PCR were applied to detect target gene expression. Oil Red O staining was applied to examinelipid accumulation in THP-1-derived macrophages. ELISA and qRT-PCR were used to examine the levels of inflammatory mediotors. We found that fargesin reduced atherosclerotic lesions by elevating efficiency of RCT and decreasing inflammatory response via upregulation of ABCA1 and ABCG1 expression in apoE−/− mice. Further, fargesin reducedlipid accumulation in THP-1-derived macrophages. Besides, fargesin increased phosphorylation of CEBPα in Ser21 and then upregulated LXRα, ABCA1 and ABCG1 expression in THP-1-derived macrophages. In addition, fargesin could reduce ox-LDL-induced inflammatory response by inactivation of the TLR4/NF-κB pathway.
Conclusion
These results suggest that fargesin inhibitsAtherosclerosis by promoting RCT process andreducing inflammatory response via CEBPαS21/LXRα and TLR4/NF-κB pathways, respectively.
Fenugreek extract
Does Fenugreek Lower Cholesterol?
There is also some evidence that fenugreek may improve heart health by keeping your lipid levels within a healthy range. Lipids are fat-like substances that can accumulate in your blood. Cholesterol and Triglycerides are both lipids.
Ficus microcarpa (L.) extract
Hypolipidaemic and antioxidant activities of Ficus microcarpa (L.) in hypercholesterolemic rats
Saponifiable and unsaponifiable fractions of Ficus microcarpa leaves hexane extract have been phytochemically studied and evaluated for its hypolipidaemic and antioxidanteffects in hypercholesterolemic rats. Theeffect of the extract on thelipid profile was assessed by measuring the levels of totalcholesterol,high-density lipoproteincholesterol (HDL-C), low-density lipoproteincholesterol (LDL-C), Triglycerides , phospho and totallipids.lipid peroxides, glutathione and superoxide dismutase were measured as antioxidants. The work was extended to evaluate liver function indices as well as the histopathological picture of the liver after treatment. Treatment with leaves extract (500 mg kg⁻¹ body weight) 5 times/week for 9 weeks at the same time ofcholesterol administration (30 mg/0.3 mL 0.7% tween/animal) recorded an improvement oflipid profile, antioxidants, liver function enzymes and the liver histopathological picture. The lipoidal matters of the unsaponifiable fraction of the hexane extract by GC/MS led to the identification of 22 compounds, while saponifiable fraction by (MS/MS) technique led to identification of 13 unsaturated and saturated fatty acid methyl ester derivatives. It can be concluded that the hexane extract of F. microcarpa L has been proved to have hypolipidaemic and antioxidanteffects in hypercholesterolemic rats through its role in counteractingLDL oxidation, enhancement of HDL synthesis and inhibition oflipid peroxidation.
Botany, Uses, Chemistry and Pharmacology of Ficus microcarpa: A Short Review
In this short review on Ficus microcarpa L. f., the first for the species, current information of the botany, uses, phytochemistry and pharmacology is presented and discussed. A common tree in coastal areas of the West Pacific region, F. microcarpa is characterised by its curtain of dangling aerial roots and small pink fruits. Considered sacred with spiritual significance, the species is an important food sources for birds and mammals, and a popular shade and ornamental plant. Used as traditional folk medicine to treat various diseases and disorders, F. microcarpa is rich in triterpenoids, phenylpropanoids, flavonoids and phenolic acids. The aerial roots are most studied, and yielded the highest number of compounds (86), notably, triterpenoids (56), phenylpropanoids (13) and phenolic acids (12). Pharmacological properties of F. microcarpa include antioxidant, antibacterial, anticancer, anti-diabetic, anti-diarrhoeal, anti-inflammatory, anti-asthmatic, hepatoprotective and hypolipidemic activities.
Objective: The present study was designed to evaluate the acute and chronic effects of the extract against alloxan induced diabetic rats. Methods: In acute study, hypoglycemic potency of methanolic extract of Ficus microcarpa was assessed by oral glucose tolerance test (OGTT) and in chronic study of 21 days, extract at different doses (ie 100, 200 and 400mg/kg) was screened for its anti-diabetic activity. Blood glucose level had been estimated at 1st, 7th, 14th and 21st and addition to this serum concentrations of insulin, Triglycerides, cholesterol, SGOT, SGPT and urea determined at 21st day of the study. Results: In OGTT, standard glibenclamide and extract (200 and 400mg/kg) have shown significant reduction in blood glucose level compared to control group. In chronic model the methanolic extract was more effective in reducing the blood glucose levels (P<0.001) and effect was comparable to that of standard. The extract could also significantly (P<0.001) reduce concentrations of SGOT, Triglycerides, cholesterol and urea in serum and significantly (P<0.001) increased the insulin level in blood which proves beneficial effects of the extract in diabetes. The change in concentrations of SGPT and urea were less significant (P>0.01). Conclusion: The methanolic extract of Ficus microcarpa posses significant antidiabetic activity in alloxan induced diabetic animal model.
Fucoidan
Application of fucoidan as treatment for cardiovascular and cerebrovascular diseases
The current guidelines for the management of dyslipidemia recommend statins as the first choice for patients with high fat [Triglycerides (TG) ⩾ 2.3 mmol/L] complicated with a high risk of CVD. However, the side effects of statins, such as myalgia, myositis, rhabdomyolysis, 6 and liver injury, cannot be ignored, and it may increase the risk of hemorrhagic stroke in patients with cerebrovascular disease. 7 Therefore, it is necessary to develop new bioactive substances. The marine biome contains highly valuable natural resources, and marine polysaccharides have a variety of biological activities. The biological activity of fucoidan and its potential applications are of particular interest.
Fucoxanthin
Increases in lymphatic and blood Triglyceride levels were much lower in the two carotenoid-treated groups than in the carotenoid-free group, indicating that these carotenoids inhibit Triglyceride absorption. The total amounts of Triglycerides released into the lymph after 4 h in the carotenoid-free, fucoxanthin and fucoxanthinol groups were 113.5, 59.4 and 53.1 micromol, respectively. The inhibitory effects of carotenoids were completely abolished after an infusion of pre-digested soybean oil containing carotenoids. Furthermore, these carotenoids inhibited pancreatic lipase activity in vitro. Regarding absorptive route, we found that fucoxanthinol, but not fucoxanthin, appeared in lymph fluid, whereas neither carotenoid was detected in portal blood.
Ganoderic Acid A
Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and Triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance.
Ganoderma lucidum extract (Ganoderma lucidum Polysaccharide)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs
Results
Organic fractions containing oxygenated lanosterol derivatives inhibitedcholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did noteffectLDL; but decreased totalcholesterol (TC) 9.8%, and HDL 11.2%. Gl (2.5 and 5%) hadeffects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC,LDL- and HDLcholesterol 20, 27, and 18%, respectively (P < 0.05); increased fecal cholestanol and coprostanol; and decreased cholate.
Conclusions
Overall, Gl has potential to reduceLDLcholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components inlipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine humancholesterollowering properties. Innovative newcholesterol-lowering foods and medicines containing Gl are envisioned.
Adenosine-rich extract of Ganoderma lucidum: A safe and effective lipid-lowering substance
Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE-/- mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), Triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.
Methods and results
Japanese big-ear white rabbits were randomly divided into three groups of blank, model, and treatment, and the treatment group was fed with GLSO and GLSP (0.3 g/kg body-weight/day) for 4 months. Serum levels of Triglyceride (TG), total (TC), and low density lipoprotein cholesterol (LDL-C) in GL treatment group were significantly lower than those in the model group. The area of aortic plaques was significantly reduced in the treatment group. Further, GL administration in oxidized low-density lipoprotein (ox-LDL) stimulated human umbilical vein endothelial cells (HUVECs) reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) by inhibiting the upregulation of the nuclear transcription factor (NF)-κB p65 and the relative receptor LOX-1. In THP-1 cells treated with phorbol myristate acetate, GL inhibited the inflammatory polarization of macrophages (as evidenced by reduced TNF-α levels) via regulation of Notch1 and DLL4 pathways. Ox-LDL-stimulated THP-1 cells treated with GL showed an increase in the apoptosis of foam cells.
Conclusions
GLTs and GLPs attenuated the progression of atherosclerosis by alleviating endothelial dysfunction and inflammatory polarization of macrophages, thus promoting apoptosis of foam cells.
Conclusions
This study revealed that G. lucidum could effectively prevent obesity and insulin resistance by attenuating adipocyte hypertrophy and dyslipidemia and improving homeostasis by recovering insulin sensitivity and adipokine function in HFD-induced obese C57BL/6 mice. In particular, G. lucidum exhibited anti-obesity activities by downregulating FAS, SCD1, and SREBP1c, and also displayed antihyperglycemic and antihyperinsulinemic activities by enhancing the activation of AMPK, ACC, IR, IRS, and Akt. Together, these results suggest that G. lucidum extract has the potential to be used as a nutritional supplement to prevent and ameliorate obesity and type 2 diabetes. Future studies should assess the effects of G. lucidum bioactive compounds on other pathways related to obesity in vivo.
Ganoderma spore powder
Diabetic rats were daily fed with a high-cholesterol diet containing 1% or 3% freeze-dried whole submerged G. lucidum culture or its mycelia for 5 weeks. Body weight, adipose tissue weight and plasma Triglyceride levels were reduced, while high-density lipoprotein-cholesterol levels were elevated in rats fed with G. lucidum powder supplement diets. Notably, G. lucidum supplements downregulated the activities of hepatic acetyl-CoA carboxylase, fatty acid synthase and lipoprotein lipase, but upregulated the activity of hormone-sensitive lipase in the perirenal adipose tissues. Moreover, G. lucidum supplements increased the faecal Triglyceride excretion. Therefore, daily supplementation of submerged G. lucidum culture, especially mycelia, can ameliorate dyslipidemia and reduce visceral fat accumulation in diabetic rats fed with a high-fat diet, which is closely related to the modulation of lipid synthesis, metabolism, and excretion.
Garcinia daedalanthera
cholesterol-lowering effects of Extract from Garcinia daedalanthera in Hyperlipidemic rats
Background: A native plant from Indonesia, Garcinia daedalanthera has been scientifically proven have antidiabeticeffects and antioxidant activity. We hypothesized that Garcinia daedalanthera can modulate thelipid profiles of hyperlipidemic rats. Objective: This study aimed to evaluate the antihyperlipidemic potential of Garcinia daedalanthera extract. Materials and Methods: Garcinia daedalanthera leaves extract (GDE) were orally administrated tohigh fatdiet-induced rats for 15 days. After the end of experimental period (43 days) thelipid profiles were estimated along with histopathological liver examination of animals. Results: The results showed that Garcinia daedalanthera extract significantly reduced the level ofserum totalcholesterol, total Triglycerides and low-density lipoprotein as compared to control group with an increasing level ofserumhigh-density lipoprotein. Furthermore, the extract has a favorableeffect on histopathological study. Conclusion: This study proved antilipidemic property bylowering altered levels oflipid profile in male wistar rats and suggestlipidloweringeffects of Garcinia daedalanthera extract which serves as a new potential natural product for preventing hyperlipidemia.
Garcinia gummi-gutta (Malabar tamarind)
In our societycholesterol related diseases are increasing day by day. The major reason for this is our eating habit or food habit. Eating foods containing trans fats, which are often found in fast food and commercially baked breads, cookies, and snack foods. It was observed that while peoples taking the fruits of Garcinia gummi-gutta in their food preparations have lowcholesterol level. Some peoples are eating boiled fruits and drinking water in which the fruits peels are boiled in order to reduce thecholesterol level. This study was carried out to explore the phytochemical constituents of the solvent extracts of Garcinia gummi-gutta fruit and in vitro analysis of itscholesterolloweringeffect. Thecholesterolloweringeffect was carried out in vitro using common fatty food materials like ghee, fats of pork and chicken, hen egg and cod liver oil. Each food materials were treated with extract and incubated for a number of days and each day thecholesterol level was estimated by Zak’s method. From the data, pork and chicken fat, egg yolk and ghee shows significant reduction in thecholesterol level. From the present study it can be concluded that the constituents present in the extracts may be responsible for thecholesterollowering activity.
Garcinia Mangostana L. Rind extract
Hypercholesterolemia contributes to the incidence of coronary heart disease which is the leading cause of death in the world 1.diet modification andhypolipidemic drugs, including herba, one of which is Garcinia mangostana L. willeffectively reduce totalcholesterol 3.
A research a posttest control group design 20, type of research was a laboratory experimental research 15. The population was male white mice aged 3 – 4 weeks weighing 100-200 grams 12. Hypercholesterolemia in male white rats was with MDLT induction (high – fatdiet food ) 7. Data collection of totalcholesterol levels measurement used enzymatic spectrophotometer method, data analysis used Variant Analysis statistical test ( ANOVA ) with significance level ? < 0.05 15.
Theeffect of Garcinia mangostana L. rind extract on totalcholesterol reduction in white rats was grouped into a negative control group, positive control group and four dose treatment groups 4. Identification of hypercholesterolaemia in white rats was examined for totalcholesterol on day 8 16. Theeffect of Garcinia Mangostana L rind extract onreducing totalcholesterol was examined on day 22 3,16 .
The results of the examination showed the administration of Garcinia mangostana L. rind extract in all dosage groupseffectively reduced totalcholesterol levels with a significance level of p < 0.05.
Obesity is one of the risk factor for dyslipidemia incident, cancer, diabetes mellitus, and cardiovascular disease. Treatment of obesity using common commercial drugs shows low rate of success, hence natural products may provide better or more efficient therapeutic approach. Mangosteen (Garcinia mangostana L.) (Clusiaceae) peel extract contains xanthones and it is potentially used as alternative medicine for obesity. This research was done to determine the anti-obesity characteristics of Mangosteen Peel Extract (MPE) and its xanthones α-Mangostin (AM) and γ-Mangostin (GM) on 3T3L1 cell line. Anti-obesity effects of MPE and xanthones were investigated using differentiated-3T3L1 preadipocyte cells. Inhibitory activity of the extract and compounds on the production of Triglyceride (TG), Cholesterol (CHOL), Glucose-6-Phosphate Dehydrogenase (G6PDH) activity, and lipid droplets were examined. MPE and its compound were capable to inhibit the production of TG, CHOL, G6PDH, lipid droplets. MPE 50 μg/mL and GM 75 μM were the most active to lower TG 57.95% and 59.72%, CHOL 33.33% and 31.68%, G6PDH 52.90%, 41.95%, lipid droplets 72.99% and 70.07% respectively. In conclusion mangosteen peel extract and γ-Mangostin are the most active antiobesity compared to α-Mangostin.
Plasma biochemistry analysis
Blood collection was performed at week 10 and week 17 of dietary intervention and kept into heparinized tubes. Blood was collected from the lateral saphenous vein at week 10 by making a puncture using a fine needle, and the blood flow was stopped by pressing gently on the puncture site. At week 17, terminal anaesthesia was induced via intraperitoneal injection of pentobarbitone sodium (Lethabarb, 100 mg/kg), and blood was drawn via cardiac puncture. Heparin (Sigma-Aldrich Australia) was administered (200 IU) through the right femoral vein. Plasma lipid profile (total cholesterol, Triglyceride, high density lipoprotein (HDL)-cholesterol and low density lipoprotein (LDL)-cholesterol) analysis was done by using diagnostic reagent test kit (Roche, Germany). Plasma glucose was determined using glucose oxidase assay kit (Sigma-Aldrich, USA) using Hitachi Automatic Analyzer (Tokyo, Japan). Plasma total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were determined using kits and controls based on manufacturer’s standard protocols (RANDOX Laboratory Ltd., USA) using a clinical chemistry analyzer machine (Vitalab Selecktra E, Germany). Plasma inflammatory markers namely alpha-tumor necrosis factor (α-TNF) and inteleukin-6 (IL-6) were analyzed using Platinum ELISA kit (eBioscience, Vienna, Austria) according to manufacturer’s instructions.
Garcinia mangostana L.has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The aim of this study was to evaluate the effect of a Mangosteen (G. mangostana L.) Pericarp Ethanolic Extract (MPEE) on lipid profile in rats fed with high-fat diet.The experimental study was conducted in male Wistar rats for 4 weeks and 9 weeks, with rats divided into 5 treatment groups which were normal (standard diet), control (high-fat diet), dose 1 (high-fat diet, MPEE 200 mg/kg b.w.), dose 2 (high-fat diet, MPEE 500 mg/kg b.w.), and orlistat (high-fat diet, orlistat 21.6 mg/kg b.w.) groups. The serum concentration of cholesterol High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL) and Triglycerides of all the animals in each group were determined after the 4 weeks and 9 weeks of treatment. Intrygliceride level, MPEE at the dose of 500 mg/kgbw was more active than the dose of 200mg/kg. The rats treated with MPEE significantly decreased the LDL level in the 9 weeks at the dose of 200 mg/kg bw and 500 mg/kg bw. However, the HDL level amongthe all groups showed no significant difference.Mangosteen Pericarp Ethanolic Extract (MPEE) has potential as anti-obesity drugs by lowering the tryglyceride and LDL level in high-fat Wistar rats.
Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid
BACKGROUND In cardiovascular medicine, Garcinia mangostana has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The effect of Garcinia mangostana on hyperlipidemia is unknown. The aim of this study was to evaluate the effect of an ethanolic extract of Garcinia mangostana pericarp on lipid profile in rats fed a high lipid diet. METHODS A total of 40 rats were divided into five groups control, high lipid diet, and high lipid diet + ethanolic extract of Garcinia mangostana pericarp at dosages of 200, 400, and 800 mg/kg body weight. The control group received a standard diet for 60 days. The high lipid diet group received standard diet plus egg yolk, goat fat, cholic acid, and pig fat for 60 days with or without ethanolic extract of Garcinia mangostana pericarp by the oral route. After 60 days, rats were anesthesized with ether for collection of blood by cardiac puncture. Analysis of blood lipid profile comprised colorimetric determination of cholesterol, Triglyceride, low density lipoprotein (LDL), and high density lipoprotein (HDL). RESULTS From the results of one-way ANOVA it was concluded that there were significant between-group differences in cholesterol, trygliceride, LDL, and HDL levels (p=0.000). Ethanolic extract of Garcinia mangostana pericarp significantly decreased cholesterol, trygliceride, and LDL levels, starting at 400 mg/kg body weight (p=0.000). Ethanolic extract of Garcinia mangostana pericarp significantly increased HDL level starting at 200 mg/kg body weight (p=0.000). CONCLUSION Ethanolic extract of Garcinia mangostana pericarp has a beneficial effect on lipid profile in rats on a high lipid diet.
The mangosteen rind (Garcinia mangostana L) contains α-mangosteen compounds. This compound is responsible for various pharmacological activities, such as antioxidants and anti-inflammatory. In this study, mangosteen rind (Garcinia mangostana L) extraction would be carried out by using three solvents with different levels of polarity (ethanol, methanol and ethyl acetate). In the current study, we aimed to identify the phytochemical content of ethanol (EEM), methanol (EMM) and, ethyl acetate (EEAM) extracts of the mangosteen rind and wanted to know the lowest reducing blood lipid effect (total cholesterol/TC and Triglycerides/TG), along with the most increasing high-density lipoprotein cholesterol (HDL-C) levels in the blood of these extract. First, the identification of compound content of EEM, EMM, and, EEAM was carried out. To increase lipid blood level, Wistar male were feed fat-rich diet (standard feed: 80%, duck egg yolk: 5% and lard: 15%) for 30 days, followed by administration of EEM, EMM, and EEAM for 30 days. On the 60th day, total cholesterol (TC), Triglyceride (TG) and high-density lipoprotein (HDL) blood measurements of the test rat were performed. The results showed that ethanol, methanol, and ethyl acetate extract contained flavonoids, terpenoids, saponins, tannins, alkaloids, and polyphenols. The pharmacological test results showed EEM, EMM, and, EEAM could reduce TC and TG levels, and were able to increase HDL-C levels in rat blood. The EEAM could reduce TC and TG levels and be able to increase HDL-C levels best compared to other extracts. This ability might be due to the highest EEAM containing alpha mangostin.
Methods
Sprague Dawley (SD) rats were fed on either AIM 93-M control diet, a high-fat diet (HFD), or high-fat diet supplemented with 25 mg/day mangosteen pericarp extract (MGE) for 11 weeks. Thereafter, the following were determined: body weight change, plasma free fatty acids, liver Triglyceride content, antioxidant enzymes (superoxide dismutase, SOD; glutathione, GSH; glutathione peroxidase, GPx; glutathione reductase GRd; catalase, CAT) and mitochondrial complex enzyme activities. In the in vitro study, primary liver cells were treated with 1 mM free fatty acid (FFA) (palmitate: oleate acid = 2:0.25) to induce steatosis. Thereafter, the effects of α-MG (10 μM, 20 μM, 30 μM) on total and mitochondria ROS (tROS, mitoROS), mitochondria bioenergetic functions, and mitochondrial pathway of apoptosis were examined in the FFA-treated primary liver cells.
Results
The MGE group showed significantly decreased plasma free fatty acids and hepatic Triglycerides (TG) and thiorbarbituric acid reactive substances (TBARS) levels; increased activities of antioxidant enzymes (SOD, GSH, GPx, GRd, CAT); and enhanced NADH-cytochrome c reductase (NCCR) and succinate-cytochrome c reductase (SCCR) activities in the liver tissue compared with HFD group. In the in vitro study, α-MG significantly increased mitochondrial membrane potential, enhanced cellular oxygen consumption rate (OCR), decreased tROS (total ROS) and mitoROS (mitochondrial ROS) levels ; reduced Ca2+ and cytochrome c (cyt c) release from mitochondria, and reduced caspases 9 and 3 activities compared with control group.
Potential roles of Garcinia family as antimetabolic syndrome
The incidence rate is directly proportional to the incidence of obesity or overweight and Type 2 diabetes mellitus. Garcinia is a plant that has been proven empirically, preclinically, and clinically to have activities for the avoidance and treatment of metabolic syndrome and on the pathogenesis and pathophysiology caused by the disease. The aim of this study is to create a discussion and summarize information regarding the activity or usefulness of the Garcinia plant. This review article was based on the published journals obtained from Google Scholar, Scopus, and PubMed databases using the keywords Garcinia obesity, Garcinia overweight, and Garcinia metabolic syndrome. Garcinia had many activities related to metabolic syndrome because it was able to reduce body fat mass, blood sugar level, body weight, total cholesterol, and Triglyceride level. These activities were mediated by numerous apparatuses of feat together with a reserve of fatty acid synthase, α-amylase, α-glucosidase, and several other enzymes and pathways associated with the metabolic syndrome. Garcinia plant was able to be used as a candidate for a new herbal that had a good effect in treating metabolic syndrome in future.
Gardenia jasminoides J. Ellis extract GJ-4
Background
GJ-4 is extracted from Gardenia jasminoides J. Ellis (Fructus Gardenia) with crocin composition and has been demonstrated to improve memory deficits in several dementia models in our previous studies.
Objective
This study aimed to evaluate theeffects of GJ-4 on hyperlipidemic vascular dementia (VD) and explore the underlying mechanisms.
Design
In the current study, we employed a chronic hyperlipidemic VD rat model by permanent bilateral common carotid arteries occlusion (2-VO) based onhigh-fatdiet (HFD), which is an ideal model to mimic the clinical pathogenesis of human VD.
Results
Our results showed that GJ-4 could significantly reduceserumlipids level and improve cerebralblood flow in hyperlipidemic VD rats. Additionally, treatment with GJ-4 remarkedlyameliorated memory impairment and alleviated neuronal injury. Mechanistic investigation revealed that the neuroprotectiveeffects of GJ-4 might be attributed to the inhibition of microglia-mediated neuro-inflammation via regulating the M1/M2 polarization. Our data further illustrated that GJ-4 could regulate the phenotype of microglia through activating the peroxisome proliferator-activated receptor-γ (PPAR-γ) and subsequently inhibited nuclear factor-κB (NF-κB) nuclear translocation and increased CCAAT/enhancer-binding protein β (C/EBPβ) expression.
Conclusion
Our results implied that GJ-4 might be a promising drug to improve VD through the regulation of microglial M1/M2 polarization and the subsequent inhibition of neuro-inflammation.
The present study was performed to investigate the hepatoprotective and hypolipidaemic effects of a 27 kDa glycoprotein isolated from Gardenia jasminoides Ellis (GJE glycoprotein) in glucose/glucose oxidase (G/GO)-treated BNL CL.2 cells, as well as in CCl4, Triton WR-1339 and corn oil-treated mice. In G/GO-treated BNL CL.2 cells, the results showed that GJE glycoprotein has an inhibitory effect on G/GO-induced cytotoxicity and intracellular reactive oxygen species production. In addition, GJE glycoprotein has an anti-oxidant effect against the lipid peroxidation process in the Fe2+/ascorbic acid system. In CCl4 (1.0 mL/kg)-treated mice, pretreatment with GJE glycoprotein (80 mg/kg) blocked lactate dehydrogenase release and the formation of thiobarbituric acid-reactive substances. In addition, in these mice GJE resulted in increased nitric oxide production and the activation of anti-oxidant enzymes, accompanied by the inhibition of the cytotoxic-related signals hepatic cytochrome c, nuclear factor-kappaB and activator protein-1. In both Triton WR-1339 (400 mg/kg) and corn oil (1.0 g/kg)-treated mice, pretreatment with GJE glycoprotein (80 mg/kg) lowered the levels of plasma lipoproteins (Triglyceride, total cholesterol and low-density lipoprotein). On the basis of these results, we assume that GJE glycoprotein can ameliorate liver function, because it has hepatoprotective and hypolipidaemic activities.
The pancreatic lipase inhibitors were isolated from the fructus of Gardenia jasminoides ELLIS, and their antihyperlipidemic activities were measured. Gardeniae fructus (GF) water extract inhibited pancreatic lipase activity. Crocetin and crocin were isolated from GF water extract as inhibitors of pancreatic lipase with an IC50 value of 2.1 and 2.6 mg/ml (triolein as a substrate). Crocin and crocetin significantly inhibited the increase of serum TG level in corn oil feeding-induced Triglyceridemic mice, as well as that of serum Triglyceride and total and LDL cholesterol levels in Triton WR-1339-induced hyperlipidemic mice. These compounds also showed hypolipidemic activity in hyperlipidemic mice induced by high cholesterol, high fat or high carbohydrate diets for 5 weeks. The results suggest that the hypolipidemic activity of GF and its component crocin may be due to the inhibition of pancreatic lipase and crocin, and its metabolite, crocetin, can improve hyperlipidemia.
Results
APP + LJH + GJE, but not APP itself, improved energy metabolism and attenuated a decrease in energy expenditure by the same amount as estrogen. Moreover, APP + LJH + GJE reduced visceral fat and intramuscular fat and increased lean body mass measured by DEXA by as much as the positive-control. APP itself suppressed increased LDL cholesterol and Triglyceride levels in OVX rats and APP + LJH + GJE alleviated dyslipidemia in OVX rats. Overnight-fasted serum insulin levels and HOMA-IR were reduced in the descending order of APP, APP + LJH, APP + LJH + GJE, positive-control in OVX rats. APP and APP + LJH elevated insulin secretion in the 1st part of OGTT to decrease serum glucose levels while APP + LJH + GJE reduced serum glucose levels without increasing serum insulin levels during OGTT. APP + LJH + GJE decreased insulin resistance during ITT in OVX rats more than the positive-control. The APP + LJH + GJE group exhibited increased hepatic peroxisomal proliferator-activated receptor-γ coactivator-1α expression, which increased the number of genes involved in fatty acid oxidation and decreased fatty acid synthesis. Hepatic insulin signaling (pAkt and pGSK-1β) was also potentiated to reduce phosphoenolpyruvate carboxykinase proteins.
Gemfibrozil
Seventeen patients in the gemfibrozil group and 16 patients in the placebo group completed the study period. Compliance was considered adequate. Mean (+/- standard deviation) plasma HDL cholesterol levels increased 20.3% (+/- 12.22) from 0.82 to 0.99 mmol L-1 in the gemfibrozil group against 9.9% (+/- 18.31) from 0.79 to 0.87 mmol L-1 in the placebo group (P = 0.001). Mean plasma Triglyceride level fell 49.5% (+/- 14.27) from 3.65 to 1.82 mmol L-1 in the gemfibrozil group against an increase of 13.6% (+/- 40.31) from 3.62 to 4.01 mmol L-1 in the placebo group (P < 0.001). Although plasma HDL cholesterol and Triglyceride levels improved in all patients, normalization of these lipoproteins was only observed in approximately half of them. Plasma total and low-density lipoprotein (LDL) cholesterol levels, as well as plasma levels of apolipoprotein (apo) A1, B100 and lipoprotein [Lp(a)], did not show significant alterations compared to the placebo. All safety parameters were comparable between the two groups and remained within the reference limits. Gemfibrozil was well tolerated during treatment. Minor inconveniences were equally distributed between the two treatment groups.
Genistein
diets containing the soya-derived phytoestrogens, genistein and daidzein, decrease plasmacholesterol in humans and experimental animals. The mechanisms responsible for the hypocholesterolaemiceffects of these isoflavones are unknown. The present study was conducted to determine if genistein and daidzein regulate hepatocytecholesterolmetabolism andapolipoprotein (apo) B secretion in cultured human hepatoma (HepG2) cells. ApoB secretion was decreased dose-dependently by up to 63% and 71% by genistein and daidzein (100 microM; P<0.0001) respectively. In contrast, noeffect on apoAI secretion was observed. Cellularcholesterol synthesis was inhibited 41% by genistein (100 microM; P<0.005) and 18% by daidzein (100 microM; P<0.05), which was associated with significant increases in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA. Cellularcholesterol esterification was decreased 56% by genistein (100 microM; P<0.04) and 29% by daidzein (100 microM; P<0.04); however, mRNA levels for acyl-CoA:cholesterol acyltransferase (ACAT) 1 and ACAT2 were unaffected. At 100 microM, both isoflavones equally inhibited the activities of both forms of ACAT in cells transfected with either ACAT1 or ACAT2. Genistein (100 microM) and daidzein (100 microM) significantly decreased the activity of microsomal triacylglycerol transfer protein (MTP) by 30% and 24% respectively, and significantly decreased MTP mRNA levels by 35% and 55%. Both isoflavones increased low-density lipoprotein (LDL)-receptor mRNA levels by 3- to 6-fold (100 microM; P<0.03) and significantly increased the binding, uptake and degradation of (125)I-labelledLDL, suggesting that enhanced reuptake of newly secreted apoB-containing lipoproteins contributed to the net decrease in apoB secretion. These results indicate that genistein and daidzein inhibit hepatocyte apoB secretion through several mechanisms, including inhibition ofcholesterol synthesis and esterification, inhibition of MTP activity and expression and increased expression of theLDL-receptor.
Results
Genistein diet significantly reduced body weight by 12% in females and 9% in males. Genistein significantly lowered serum glucose levels by 18% in females and 43% in males, yet had no effect on serum insulin. Genistein diet significantly lowered serum Triglyceride levels in both ob/ob male and female mice returning them to lean levels. In females only, genistein significantly reduced serum pancreatic polypeptide levels by 56% and increased serum GIP levels 2.3-fold. Genistein had sex-dependent effects on hepatic steatosis: in females, genistein further increased the % fat area and the fat droplet diameter 2.6-fold, along with additionally increasing hepatic TBARS.
Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis
Results: Eight randomized, controlled trials with a total of 476 subjects were included in the meta-analysis. Compared with placebos, genistein was effective in reducing plasma levels of homocysteine (WMD, −0.58 μmol/l; p = 0.001), and increasing high density lipoprotein (HDL) cholesterol levels (WMD, 4.9 mg/dl; p = 0.0002). Subgroup analyses revealed that genistein significantly decreased the levels of low density lipoprotein (LDL) cholesterol (WMD, −16.90 mg/dl; p = 0.01), total cholesterol (WMD, −15.83 mg/dl; p = 0.008), and Triglycerides (WMD, −46.58 mg/dl; p = 0.03) in postmenopausal women with metabolic syndrome, but had no significant effects in those with no metabolic syndrome.
Conclusions: Our meta-analysis demonstrates that genistein significantly reduces homocysteine levels and increases HDL cholesterol levels in postmenopausal women. Genistein also significantly decreases LDL cholesterol, total cholesterol and Triglyceride levels in postmenopausal women with metabolic syndrome.
Genistein in the Metabolic Syndrome: Results of a Randomized Clinical Trial
In genistein recipients, we observed a decrease in Triglycerides, total cholesterol, and LDL-C, with a corresponding increase in HDL-C, after 6 months and 1 year of treatment. The positive effect of genistein on lipid metabolism was further supported by a significant reduction in waist circumference that could be related, at least in part, by an enhanced fatty acid catabolism in liver cells, as recently shown in obese animals.
Ginger
BACKGROUND
Although the antioxidant properties of ginger have been revealed, there is little available information on theeffectiveness of ginger on inflammatory disorders such asAtherosclerosis. This study was carried out to examine theeffect of ginger on improving the complication ofAtherosclerosis.
METHODS
This study was a double-blind, placebo-controlled, randomized clinical trial conducted on patients withAtherosclerosis. Participants in the ginger and control groups received 1600 mg of powdered ginger or placebo (wheat flour) in capsules daily for 8 weeks. Weight, body mass index (BMI), fastingblood sugar (FBS),cholesterol, Triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL),high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)],high-sensitivity C-reactive protein (hs-CRP), and total anti-oxidant capacity (TAC) were assessed before and after the intervention.
RESULTS
Ginger consumption in the intervention group significantly reducedserum Lp(a) level (27.25 ± 1.30 ng/ml vs. 23.57 ± 0.97 ng/ml) (P = 0.040) and also the level of hs-CRP in the intervention group was 1.90 ± 0.33 µg/ml and 1.24 ± 0.15 µg/ml (P = 0.010) before and after intervention, respectively, but the levels of Lp(a) and hs-CRP were not decreased significantly in the placebo group. The level of TAC in the ginger group was 0.71 ± 0.05 mM and after the trial was 0.57 ± 0.04 mM (P = 0.050); no significant differences were seen in TAC when ginger was administered at 1600 mg/daily for 60 days. Also the level of Lp(a) and hs-CRP but not TAC reduced significantly in ginger group compared to placebo group after intervention.
CONCLUSION
This study showed that ginger had anti-Atherosclerosis and anti-glycemic properties associated through a significant decreased Lp(a) and FBS in patients withAtherosclerosis supplemented with ginger.
Diabetes mellitus is the most common endocrine disorder, causes many complications such as micro- and macro-vascular diseases. Anti-diabetic,hypolipidemic and anti-oxidative properties of ginger have been noticed in several researches. The present study was conducted to investigate theeffects of ginger on fastingblood sugar, Hemoglobin A1c,apolipoprotein B,apolipoprotein A-I, and malondialdehyde in type 2 diabetic patients. In a randomized, double-blind, placebo-controlled, clinical trial, a total of 41 type 2 diabetic patients randomly were assigned to ginger or placebo groups (22 in ginger group and 19 in control group), received 2 g/day of ginger powder supplement or lactose as placebo for 12 weeks. Theserum concentrations of fastingblood sugar, Hemoglobin A1c,apolipoprotein B,apolipoprotein A-I and malondialdehyde were analyzed before and after the intervention. Ginger supplementation significantly reduced the levels of fastingblood sugar, hemoglobin A1c,apolipoprotein B,apolipoprotein B/apolipoprotein A-I and malondialdehyde in ginger group in comparison to baseline, as well as control group, while it increased the level ofapolipoprotein A-I (p<0.05). It seems that oral administration of ginger powder supplement can improves fastingblood sugar, hemoglobin A1c,apolipoprotein B,apolipoprotein A-I,apolipoprotein B/apolipoprotein A-I and malondialdehyde in type 2 diabetic patients. So it may have a role in alleviating the risk of some chronic complications of diabetes.
BACKGROUND
Although the antioxidant properties of ginger have been revealed, there is little available information on theeffectiveness of ginger on inflammatory disorders such asAtherosclerosis. This study was carried out to examine theeffect of ginger on improving the complication ofAtherosclerosis.
METHODS
This study was a double-blind, placebo-controlled, randomized clinical trial conducted on patients withAtherosclerosis. Participants in the ginger and control groups received 1600 mg of powdered ginger or placebo (wheat flour) in capsules daily for 8 weeks. Weight, body mass index (BMI), fastingblood sugar (FBS),cholesterol, Triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL),high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)],high-sensitivity C-reactive protein (hs-CRP), and total anti-oxidant capacity (TAC) were assessed before and after the intervention.
RESULTS
Ginger consumption in the intervention group significantly reducedserum Lp(a) level (27.25 ± 1.30 ng/ml vs. 23.57 ± 0.97 ng/ml) (P = 0.040) and also the level of hs-CRP in the intervention group was 1.90 ± 0.33 µg/ml and 1.24 ± 0.15 µg/ml (P = 0.010) before and after intervention, respectively, but the levels of Lp(a) and hs-CRP were not decreased significantly in the placebo group. The level of TAC in the ginger group was 0.71 ± 0.05 mM and after the trial was 0.57 ± 0.04 mM (P = 0.050); no significant differences were seen in TAC when ginger was administered at 1600 mg/daily for 60 days. Also the level of Lp(a) and hs-CRP but not TAC reduced significantly in ginger group compared to placebo group after intervention.
CONCLUSION
This study showed that ginger had anti-Atherosclerosis and anti-glycemic properties associated through a significant decreased Lp(a) and FBS in patients withAtherosclerosis supplemented with ginger.
Antihypercholesterolaemic effect of ginger rhizome (Zingiber officinale) in rats
Methods: 48 rats were used throughout the experiment, which were divided into six groups, eight animals each as follows: normal control group (normal rats which fed with standard diet). After induction of hypercholesterolaemia by feeding rats with high cholesterol diet, the remaining rats were divided into five groups: group 1, hypercholesterolaemic control group (hypercholesterolaemic rats group); groups 2, 3 and 4, rats were given aqueous infusion of ginger (100, 200 and 400 mg/kg, respectively) orally; and group 5, rats were given atorvastatin (0.18 mg/kg) orally as a reference antihypercholesterolaemic drug. The blood was obtained from all groups of rats after being lightly anaesthetized with ether and the following lipid profile [serum total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-C and Triglyceride levels] was measured at zero time and 2 and 4 weeks after ginger and atorvastatin treatment, and the risk ratio (TC/HDL-cholesterol) was assessed.
The effect of ginger (Zingiber Officinale) as an ancient medicinal plant on improving blood lipids
Methodology
The information in this narrative review is obtained based on the results of the authors search in Pubmed, Google scholar, and Science Direct databases by using the keywords “ginger and Zingiber officinale” in combination with “lipid, cholesterol, Triglyceride, and diabetes” without considering any time limitation. All relevant human studies (clinical trials) were included and discussed in this paper.
Results
Our data indicate that the intracellular lipid accumulation decreased significantly by 15 or 25% on treatment with 25 or 50 μg/mL of ginger extract. Consistent with these data, significantly reduced Triglyceride levels by 30 or 50% were observed on 25 or 50 μg/mL treatment with ginger extracts, respectively. In addition, ginger treatment significantly inhibited the differentiation-induced de novo lipogenesis and Δ9 desaturase activity. Furthermore, ginger treatment reduced adipogenesis genes, C/ebpβ and C/ebpδ, expression by 47 or 64%, respectively, but significantly increased Pparγ expression by 60% and adiponectin by 75%. Ginger extracts had no effect on Fas genes but reduced lipogenesis genes, acyl CoA carboxylase (Acc) expression by two-fold, and phosphoenolpyruvate carboxy kinase 1 (Pepck1) expression by 50%.
Conclusion
Our findings suggest immature ginger can potentially inhibit lipogenesis pathways by limiting the channeling of glucose carbon in fatty acid synthesis by inhibiting the expression of ACC and glycerol production via inhibiting the expression of PEPCK, which consequently inhibits Triglyceride formation.
Ginkgo biloba L leaves extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Ginkgo biloba extract prevents ethanol induced dyslipidemia
Ginkgo biloba extract (EGB) functions as a natural substantial antioxidant and hypolipidemic. Chronic alcohol abuse leads to sustained dyslipidemia characterized by hyperlipidemia and lipid peroxidation. Thus, the present study investigates the effect of EGB on lipid disorders induced by ethanol in rats. Male Sprague-Dawley rats were fed with ethanol (2.4 g/kg), and pretreated with a daily dose of low or high EGB (48 or 96 mg/kg, respectively). During the experiment, serum was collected on day 30, 60, and 90. Serum lipid profile, including lipid peroxidation, was determined by colorimetric methods. Our data showed that ethanol intake resulted in a time-dependent increase in serum levels of Triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and malondialdehyde (MDA), and a decrease of the ratio of high-density lipoprotein cholesterol (HDL-C) against TC. EGB prophylactic medication (48 and 96 mg/kg), especially at the high dose, significantly increased HDL-C content, and normalized the abnormal lipid profile and peroxidation in comparison to ethanol-fed only rats. These results suggest that ethanol results in time-dependent hypercholesterolemia, hyperTriglyceridemia and promotes serum lipid peroxidation. EGB pretreatment prevents hyperlipidemia and ameliorates lipid peroxidation induced by ethanol.
Diabetes mellitus (DM) is caused by either destruction of pancreatic β-cells (type 1 DM) or unresponsiveness to insulin (type 2 DM). Conventional therapies for diabetes mellitus have been developed but still needs improvement. Many diabetic patients have complemented conventional therapy with alternative methods including oral supplementation of natural products. In this study, we assessed whether Ginkgo biloba extract (EGb) 761 could provide beneficial effects in the streptozotocin-induced type 1 DM and high-fat diet-induced type 2 DM murine model system. For the type 1 DM model, streptozotocin-induced mice were orally administered EGb 761 for 10 days prior to streptozotocin injection and then again administered EGb 761 for an additional 10 days. Streptozotocin-treated mice administered EGb 761 exhibited lower blood Triglyceride levels, lower blood glucose levels and higher blood insulin levels compared to streptozotocin-treated mice. Furthermore, liver LPL and liver PPAR-α were increased whereas IL-1β and TNF-α were decreased in streptozotocin-injected mice treated with EGb 761 compared to mice injected with streptozotocin alone. For the type 2 DM model, mice were given high-fat diet for 60 days and then orally administered EGb 761 every other day for 80 days. We found that mice given a high-fat diet and EGb 761 showed decreased blood Triglyceride levels, increased liver LPL, increased liver PPAR-α and decreased body weight compared to mice given high-fat diet alone. These results suggest that EGb 761 can exert protective effects in both type 1 and type 2 DM murine models.
Ginseng Extract
Ginseng has been used in herbal medicine over centuries (Koehn and Carter, 2005). It has been recognized as a medicinal herb in traditional Chinese medicine as mentioned in the Shennong Bencao Jing and in the Shang-Han Lun (Park et al., 2012b). Actually, Chinese, Korean and Japanese traditional herbal formulas that include ginseng, for example, Chai-Hun-Jia-Long-Gu-Muli-Tang, have shown protective effects against atherosclerosis (Yoshie et al., 2001). Additionally, Shenqi, which is a traditional formulation that contains ginseng, was able to reduce blood total cholesterol and Triglyceride levels in diabetic patients (Yang and Wang, 2000); suggesting that ginseng may be useful for the treatment of metabolic disorders.
Globularia alypum L
The beneficial healtheffects of plant polyphenols were frequently attributed to their powerful hypolipemiant and antioxidanteffects. We hypothesized that administration of Globularia alypum (Ga) lyophilized methanolic extract wouldameliorate glycemia,lipid parameters,reversecholesteroltransport, as well as lipoproteins peroxidation, in diabetic rats. Diabetes was induced in male Wistar rats, weighing 250±10 g by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight). Diabetic rats (n=20) were divided into two groups, and fed during 4 weeksdiets containing 20% casein (D) or a caseindiet supplemented with a Ga extract (1 g/kg BW) (DGa). At d28, in DGa vs D group, glycemia was lowered by 81%, while insulinemia was markedly increased by 72%. Liver andserumlipid values were significantly decreased (P< 0.05). Lecithin:cholesterol acyltransferase (LCAT) activity wasimproved (+48%). Indeed, HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) concentrations were respectively reduced by 50 and 52%, whereas HDL2-CE values (product of LCAT reaction) were increased (+35%). Atherogenicity ratios VLDL-LDL-C/HDL-C, TC/HDL-C and apoB/apoA were lowered respectively by 50%, 25% and 71%. Moreover, VLDL-LDL and HDL3peroxidation was decreased by 47 and 75%, respectively.In STZ-induced diabetic rat, Globularia alypum extract reduces glycemia, liver andserumlipids values, VLDL-LDL and HDL3lipid peroxidation andameliorates thereversecholesteroltransport. Therefore, Ga extract may be useful for preventing diabetes andlipid disorders.
The beneficial health effects of plant polyphenols were frequently attributed to their powerful hypolipemiant and antioxidant effects. We hypothesized that administration of Globularia alypum (Ga) lyophilized methanolic extract would ameliorate glycemia, lipid parameters, reverse cholesterol transport, as well as lipoproteins peroxidation, in diabetic rats. Diabetes was induced in male Wistar rats, weighing 250±10 g by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight). Diabetic rats (n=20) were divided into two groups, and fed during 4 weeks diets containing 20% casein (D) or a casein diet supplemented with a Ga extract (1 g/kg BW) (DGa). At d28, in DGa vs D group, glycemia was lowered by 81%, while insulinemia was markedly increased by 72%. Liver and serum lipid values were significantly decreased (P< 0.05). Lecithin:cholesterol acyltransferase (LCAT) activity was improved (+48%). Indeed, HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) concentrations were respectively reduced by 50 and 52%, whereas HDL2-CE values (product of LCAT reaction) were increased (+35%). Atherogenicity ratios VLDL-LDL-C/HDL-C, TC/HDL-C and apoB/apoA were lowered respectively by 50%, 25% and 71%. Moreover, VLDL-LDL and HDL3peroxidation was decreased by 47 and 75%, respectively.In STZ-induced diabetic rat, Globularia alypum extract reduces glycemia, liver and serum lipids values, VLDL-LDL and HDL3 lipid peroxidation and ameliorates the reverse cholesterol transport. Therefore, Ga extract may be useful for preventing diabetes and lipid disorders.
Fructose is widely used as a food ingredient and has potential to increase oxidative stress. Moreover, the beneficial health effects of plant polyphenols are frequently attributed to their potent antioxidant effects. We hypothesized that administration of Globularia alypum (Ga) aqueous extract would reduce metabolic disorders and oxidative stress induced in rats fed a high-fructose diet. Male Wistar rats (n = 24) weighing 242 ± 13 g were divided into 4 groups and fed, during 14 week, diets containing 20% casein and 61% cornstarch (control diet, or C) or fructose (F), and Ga supplementation (0.5%; CGa and FGa). Compared with control group, rats fed a high-fructose diet increased plasma Triglycerides (TG; +48%) and very low-density lipoprotein-TG (+45%) levels. In addition, thiobarbituric acid reactive substances were increased in the liver (+31%), heart (+55%), and muscle (+58%). Moreover, activities of superoxide dismutase in the liver and heart, catalase in liver and glutathione peroxidase in the heart were diminished. In the FGa group, a hyperTriglyceridemic effect was observed concomitantly with a low level of TG in very low-density lipoprotein and high-density lipoprotein 2, compared with the F group. Thiobarbituric acid reactive substance concentrations were reduced in the kidney (-42%)and muscle (-76%), and antioxidant enzymes activity was increased for superoxide dismutase in the muscle (+81%) and heart (+28%), and for glutathione peroxidase, in the kidney (+70%) and heart (+30%). In conclusion, the Ga extract has a beneficial effect on plasma TG and gives a promising perspective for hyperTriglyceridemia treatment. Moreover, in the muscle and kidney, Ga is effective by lowering lipid peroxidation and improves antioxidant enzymes.
Purpose This paper aims to investigate the preventive effects of a concomitant supplementation of a lyophilized aqueous extract of Globularia alypum (Ga) leaves in a high cholesterol-diet (HC-D) on lipid profile and lecithin cholesterol acyltransferase (LCAT) activity in hypercholesterolemic rats. Design/methodology/approach Twenty-four male Wistar rats weighing 232 ± 10 g were divided into four groups (n = 6). Two control groups were fed a standard-diet (St-D) supplemented (C- Ga ) or not (C) with 1.66% Ga leaf extract. The two others experimental groups were fed HC-D, which contains the St-D plus 1% of cholesterol and 0.5% of cholic acid supplemented (HC- Ga ) or not (HC) with the same amount of Ga . At d28, feces were collected and fasting rats were anesthetized; bloods and livers were removed to measure biochemical parameters. Findings In hypercholesterolemic (HC) rats, Ga supplementation in HC-D induced a significant reduction in ALT (−64%, p = 0.002) and AST (−71%; p = 0.005) activities, in plasma TC (−55%; p = 0.03) and TG (−54%; p = 0.01) concentrations, in cholesterol contents of atherogenic lipoproteins VLDL (−78%; p = 0.004) and LDL-HDL1 (−64%; p = 0.003) and inversely, an increase in those of anti-atherogenic HDL2 (+14%; p = 0.002). Feeding the HC-D-Ga exhibited a reduction in atherogenic index Apo B/Apo A-I (−72%; p = 0.002), an increase in faecal lipids, cholesterol excretion and in plasma apo A-I (+60%; p = 0.002) and HDL2-cholesteryl esters (+32%, p = 0.04) and then improved LCAT activity (+31%; p = 0.03). Originality/value In hypercholesterolemic rats, Globularia alypum extract was effective in preventing lipid disorders by its hypolipidemic action, had an anti-atherogenic potential and a protective effect against cardiovascular risk by enhancing LCAT activity.
The present study investigates the effect of intraperitoneal administration of Globularin on blood glucose levels in normal and streptozotocin diabetic rats. Globularin was an iridoid glucoside which was isolated from the leaves of Globularia alypum (3.4 %). This compound was identified by means of physical constants and spectral data UV, IR, MS, 1H-NMR, 13C-NMR, DEPT, COSY, HMBC. The acute toxicity test demonstrated that Globularin is not lethal up to dose of 1000 mg/kg body weight after intraperitoneal injection. In normal and streptozotocin diabetic rats, single intraperitoneal administration of Globularin at a dose 100 mg/kg body weight produced significant decrease of blood glucose levels. However, in prolonged treatment study, the repeated intraperitoneal administration of Globularin (2 x 100 mg/kg body weight) decreased significantly the blood glucose levels when compared to the diabetic control rats. In addition, daily injection of Globularin (2 x 100 mg/kg body weight) reduced significantly serum levels of total cholesterol (varied from 0.53 to 0.41 g/L) and Triglycerides (varied from 1.71 to 0.79 g/L) in the diabetic rats.
Glycyrrhiza glabra L.
Atheroprotectiveeffects of Glycyrrhiza glabra L.
Cardiovascular diseases associated withAtherosclerosis are the major cause of death in developed countries. Early prevention and treatment ofAtherosclerosis are considered to be an important aspect of the therapy of cardiovascular disease. Preparations based on natural products affect the main pathogenetic steps of atherogenesis, and so represent a perspective for the long-term prevention ofAtherosclerosis development. Numerous experimental and clinical studies have demonstrated the multiple beneficialeffects of licorice and its bioactive compounds—anti-inflammatory, anti-cytokine, antioxidant, anti-atherogenic, and anti-platelet action—which allow us to consider licorice as a promising atheroprotective agent. In this review, we summarized the current knowledge on the licoriceAnti-atherosclerotic mechanisms of action based on the results of experimental studies, including the results of the in vitro study demonstrating licoriceeffect on the ability ofbloodserum to reduce intracellularcholesterol accumulation in cultured macrophages, and presented the results of clinical studies confirming the ameliorating activity of licorice in regard to traditional cardiovascular risk factors as well as the directAnti-atheroscleroticeffect of licorice.
The present study was to investigate the anti-obesity effects of the freeze dried powder of ethanolic extract of Licorice (Glycyrrhiza Glabra) (LP) in a rat model of high-fat diet induced obesity and hyperlipidemia. Male wistar rats were fed with a high-fat diet for 8 weeks to induce obesity and hyperlipidemia. High fat diet induced obese rats exhibited increases in body weight gain, adipose tissue mass and levels of serum glucose, Triglycerides and total cholesterol compared to rats fed a normal chow diet. However, administration of LP (100-400 mg/kg, o.d., p.o) along with high-fat diet for 8 weeks significantly reduced high fat diet-induced increases in body weight gain and adipose tissue mass in a dose dependant manner. Moreover, LP attenuated high fat diet induced increased levels of serum glucose, Triglycerides and total cholesterol. The antiobesity effects of LP were comparable to orlistat, a well reported pancreatic lipase inhibitor. The antiobesity activity of LP appears to be mediated by decreasing dietary fat absorption from the intestine as LP dose dependently attenuated the raising of the serum Triglycerides level after oral lipid load test and enhanced excretion of fecal fat.
This study was undertaken to assess the effect of Glycyrrhiza glabra root extract (GGE) on the plasma lipid profile of rats. Thirty male albino rats weighing between 150 g and 170 g were used for this investigation. Rats fed 150, 250 and 400 mg/kg (GGE) for a period of 60 days showed significantly (p < 0:05) decreased the levels of total cholesterol (TC),total low density lipoprotein (LDL) and total Triglycerides (TG) cholesterol on the other hand increased the level of high density lipoprotein (HDL) cholesterol in compared with positive control fed high cholesterol diets HCD.
The recent studies have shown the effect of ethnomedicinal plants on the treatment of fatty liver disease. The purpose of the experiment was to survey the remedial activity of Glycyrrhiza glabra aqueous extract on high-fat diet-induced hepatotoxicity in rats. The synthesized extract had great cell viability dose-dependently, and this method was found to be non-toxic for synthesizing G. glabra. In the study, a total of 10 rats were chosen as the negative control, and 40 rats were treated with a high-fat diet for 4 months. Then, the animals were randomly divided into five subgroups, including negative healthy control, untreated negative control, and three groups receiving the G. glabra aqueous extract at 20, 60, and 180 mg/kg concentrations. After 2 months, the rats were sacrificed, and blood and liver samples of them collected. Different groups of G. glabra could significantly (p ≤ 0.05) decrease the increased concentrations of ALP, AST, ALT, GGT, cholesterol, LDL, Triglyceride, total and conjugated bilirubin, and glucose, and enhance HDL, total protein, albumin, SOD, and CAT as compared to the untreated group. Also, G. glabra reduced the degree of hepatic steatosis as compared to the untreated group. It appears that the G. glabra aqueous extract can treat fatty liver disease in rats without any side effect.
Atheroprotective Effects of Glycyrrhiza glabra L.
It is known that the expression of paraoxonase 2 (PON2) increases in monocytes during their differentiation into macrophages as a result of NADPH oxidase activation [46]. Therefore, the reduced expression of PON2 observed in hypercholesterolemia may be due to increased macrophage cholesterol rather than increased oxidative stress. Therefore, an increase in PON2 expression can be considered a selective cellular response that contributes to a decrease in oxidative load formation of foam cells [47]. It has also been shown that glabridin increases the expression of PON2 mRNA and protein, which, in turn, reduces oxidative stress and Triglyceride accumulation in macrophages and endothelial cells
Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18β-glycyrrhizic acid (18β-GA), is the main active ingredient of licorice. GA is generally considered an effective pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18β-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18β-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18β-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18β-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total Triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18β-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18β-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.
Liquiritigenin (LQG) is a natural flavonoid from the herb Glycyrrhiza uralensis Fisch that exhibits multiple biological activities. However, its specific role in antiobesity and its related underlying molecular mechanisms remain unknown. The primary purpose of this study is to explore the effects and regulatory mechanisms of LQG on lipid accumulation in 3T3-L1 adipocytes. The results show that LQG significantly reduced Triglyceride levels and downregulated the expression of transcription factors such as CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) in 3T3-L1 adipocytes. Additionally, the expression of sterol-regulatory element-binding protein 1c (SREBP1c), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN) involved in lipogenesis was reduced by treatment with LQG. The protein expression levels of light chain 3B (LC3B), autophagy-related protein 7 (ATG7) and p62 were also modulated by LQG, leading to the suppression of autophagy. Further, LQG activated the phosphorylation of the mammalian target of rapamycin (mTOR), the inhibition of which was followed by the restored expression of autophagy-related proteins. Pretreatment with an mTOR inhibitor also reverted the expression of several genes or proteins involved in lipid synthesis. These results suggest that LQG inhibited lipid accumulation via mTOR-mediated autophagy in 3T3-L1 white adipocytes, indicating the role of LQG as a potential natural bioactive component for use in dietary supplements for preventing obesity.
Grape seed extract
Oligomeric Proanthocyanidins: An Updated Review of Their Natural Sources, Synthesis, and Potentials
Hyperlipidemia, as one of the risk factors of obesity, is also one of the important pathogenic factors of CVD, and OPCs have been proven to have a certain effect in reducing the content of blood lipids, for example, dimer OPCs from Iris lactea Pall. var. Chinensis (Fisch.) Koidz (I. lactea) can effectively inhibit the formation of fat and also reduce Triglycerides, total cholesterol, and LDL [99]. One of the reasons why OPCs to be lower blood lipids, and the risk of hyperlipidemia is reduced from that OPCs can inhibit the increase in the expression of microRNAs (miRNA), miR-33 and miR-122, which are two important factors that can affect lipid metabolism, in dyslipidemic obese rats [100]. In addition, OPCs inhibit or slow down the uptake of lipids and lipase activity by increasing the rate of lipid β oxidation through the AMPK pathway, accelerating cholesterol breakdown, and reducing the de novo synthesis of fat
Green tea extract Tea polyphenol
cholesterol-lowering effect of a Theaflavin-Enriched Green Tea Extract
Background Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoproteincholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact onlipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on thelipids and lipoproteins of subjects with mild to moderate hypercholesterolemia.
Methods Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fatdiet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in totalcholesterol,LDL-C,high-density lipoproteincholesterol (HDL-C), and Triglyceride levels compared with baseline.
Results After 12 weeks, the mean ± SEM changes from baseline in totalcholesterol,LDL-C, HDL-C, and Triglyceride levels were −11.3% ± 0.9% (P = .01), −16.4% ± 1.1% (P = .01), 2.3% ± 2.1% (P = .27), and 2.6% ± 3.5% (P = .47), respectively, in the tea extract group. The mean levels of totalcholesterol,LDL-C, HDL-C, and Triglycerides did not change significantly in the placebo group. No significant adverse events were observed.
Conclusion The theaflavin-enriched green tea extract we studied is aneffective adjunct to a low-saturated-fatdiet to reduceLDL-C in hypercholesterolemic adults and is well tolerated.
Guggulsterone
Pharmacological importance of the active molecule “guggulsterone” in overall human health
Guggulipid has a long history of use in Ayurvedic medicine, which is an ancient Indian system that uses an integrated approach (diet, lifestyle, herbs, exercise, and meditation) to the prevention and treatment of illness by maintaining harmony among the mind, body, and forces of nature. Both guggul and its purified extracts have been used as hypolipidemic agents in patients with ischemic heart disease, hypercholesterolemia, and obesity (214). Clinical studies performed in India have demonstrated that 25 mg of guggulsterone extracts t.i.d. may be an effective treatment for hypercholesterolemia and hyperTriglyceridemia. Reductions in total cholesterol levels of approximately 24% and reductions in Triglycerides of 16% to 23% have been reported (215,216). The majority of these trials were not randomized.
Gymnema sylvestre R. Br. leaf extract
Gymnema sylvestre R. Br. leaf extract (25–100 mg/kg) when orally administered to experimentally induced hyperlipidaemic rats for 2 weeks, reduced the elevatedserum Triglyceride (TG), totalcholesterol (TC), very low-density lipoprotein (VLDL)-and low-density lipoprotein (LDL)-cholesterol in a dose-dependent manner. The decreasedserumhigh-density lipoprotein (HDL)-cholesterol and antiatherogenic index (AAI) in hyperlipidaemia were alsoreversed towards normalization. The ability of this extract (at 100 mg/kg) to lower Triglyceride and TC inserum and itsAntiatherosclerotic potential were almost similar to that of a standardlipidlowering agent—clofibrate.
A systematic review of Gymnema sylvestre in obesity and diabetes management
The prevalence of obesity is associated with many health-related problems. Currently, more than 300 million people are considered to be obese. According to the World Health Organization (WHO), by 2030, 87 and 439 million people will be affected in India and the world, respectively. Today, herbal medicines are gaining interest in the treatment of obesity and diabetes, because of their minimal side effects. Gymnemic acid – an active component isolated from Gymnema sylvestre – has anti-obesity and antidiabetic properties, decreases body weight and also inhibits glucose absorption. Several components extracted from Gymnema prevent the accumulation of Triglycerides in muscle and liver, and also decrease fatty acid accumulation in the circulation. In this paper, an attempt has been made to review the effects of various extracts from Gymnema sylvestre in the regulation of carbohydrate and lipid metabolism in both animal and clinical studies.
Results
STZ-diabetic rats exhibited a significant increase in plasma glucose, liver function enzymes [alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST)], Triglycerides, total cholesterol, LDL-cholesterol malondialdehyde, catalase, reduced glutathione and a significant decrease in insulin, HDL-cholesterol and erythrocyte superoxide dismutase levels. Treatment diabetic rats with G. sylvestre leaves extract significantly decreased plasma glucose, ALT, AST, Triglycerides, total cholesterol, LDL-cholesterol, malondialdehyde and significantly increased insulin, HDL-cholesterol and erythrocyte superoxide dismutase levels compared to untreated diabetic rats.
This systematic review and meta-analysis aims to find the effect of Gymnema sylvestre (GS) supplementation on glycemic control in type-2 diabetes mellitus (T2DM). PubMed, Cochrane library, Google Scholar, and Science Direct were searched from inception to June 2020 to identify the studies that reported GS supplementation on glycemic parameters. Standardized mean difference (SMD) was calculated by comparing the post-intervention data with baseline data. SMDs with 95% confidence intervals (CIs) were pooled using a random-effects model. Our meta-analysis consisting of 10 studies with a total of 419 participants showed that GS supplementation significantly reduces fasting blood glucose (FBG) (SMD 1.57 mg/dl, 95% CI 2.22 to −0.93, p < .0001, I2 90%), postprandial blood glucose (PPBG) (SMD 1.04 mg/dl, 95% CI 1.53 to −0.54, p < .0001, I2 80%), and glycated haemoglobin (HbA1c) (SMD 3.91, 95% CI 7.35 to −0.16%, p < .0001, I2 99%) compared to baseline. Further, our study also found that GS significantly reduces Triglycerides (SMD 1.81 mg/dl, 95% CI 2.95 to −0.66, p < .0001, I2: 96%), and total cholesterol (SMD 4.10 mg/dl, 95% CI 7.21 to −0.99, p < .0001, I2: 98%) compared to baseline. Our study shows that GS supplementation is effective in improving glycemic control and reducing lipid levels in T2DM patients and suggests that such supplementation might be used as an effective therapy for the management of T2DM and its associated complications to an extent.
Gymnema sylvestre: An Alternative Therapeutic Agent for Management of Diabetes
Gymnema sylvestre (Asclepiadaceae) also known as ‘gurmar’ or ‘sugar destroyer’ is a woody, climbing traditional medicinal herb which has many therapeutic applications in Ayurvedic system of medicine. It is used for lowering serum cholesterol, Triglycerides and blood glucose level (hypoglycemic or antihyperglycemic), hypolipidaemic, weight loss, stomach ailments, constipation, water retention and liver diseases, either high or low blood pressure, tachycardia or arrhythmias, and used as aperitive, purgative, in eye troubles, anti inflammatory, smooth muscle relaxant, prevention of dental caries, cataract and as anticancer-cytotoxic agent. Its flowers, leaves, and fruits contains alkaloids, flavones, saponins, sapogenins, anthraquinones, hentri-acontane, pentatriacontane, α and β-chlorophylls, phytin, resins, d-quercitol, tartaric acid, formic acid, butyric acid, lupeol, β-amyrin related glycosides and stigmasterol having main principle bioactive compunds viz. gymnemic acids, gymnemasides, gymnemagenin, gurmarin, gymnemosides, gymnemanol, gymnemasins, gypenoside, and conduritol which act as therapeutic agent and play vital role in many therapeutic applications. Gymnemic acids are thought to be responsible for its antidiabetic activity and it is the major component of an extract shown to stimulate insulin release from the pancreas. Another anti-sweet agent gumarin is utilized as a pharmacological tool in the study of sweet-taste transduction. The commercial exploitation of this plant and their secondary metabolites are some of the major prospective of this rare medicinal herb. The focus of the present review is to achieve the potential of therapeutic value of this herb and mechanism and action of their secondary metabolites.
Gynostemma pentaphyllum (Thunb.) Makino extract Gypenosides
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
This study characterized chemical structures of tetraploid jiaogulan saponins, and investigated theircholesterol-lowering effects and mechanisms in hamsters fed ahigh-fatdiet (HFD). Nine saponins, including five reported for the first time, were obtained from total jiaogulan saponins (TJS) and elucidated for their chemical structures according to 2D NMR and HR-MS data. Administration of TJSeffectively decreased plasma totalcholesterol by 17.4% and 32.6%, triacylglycerols by 22.8% and 47.7% andLDL-C by 22.0% and 40.2%, respectively. Moreover, supplementation with TJS significantly increased faecal excretion of totalcholesterol and bile acids by 43.8% and 64.4%, respectively. TJS significantly up-regulated intestinal mRNA levels of ABCG5/8, LXRα, hepatic mRNA CYP7A1 and ABCG5 in hamsters on HFD. In addition, TJS decreasedcholesterol micelle solubility and suppressedcholesterol uptake in cultured Caco-2 cells. Taking together, TJS may reduce plasmacholesterol by increasing faecalcholesterol excretion and through modulation of genes involved incholesterolabsorption andmetabolism.
Results
Only 101 G. pentaphyllum compounds have been initially explored for their hypolipidemic activity. There are cell models, animal models and human subjects for lipid-lowering of it. It reduced Triglyceride level via PPAR/UCP-1/PGC-1α/PRDM16 and (SREBP-1c)-ACC/FAS-CPT1 signal pathways. Cholesterol-lowering effects via (SREBP-2)-HMGCR, PCSK9-LDLR and bile acid biosynthetic pathways. Activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) is a key factor in the regulation of glycolipid metabolism in G. pentaphyllum. Other pathways of action of G. pentaphyllum in regulating glucolipid metabolism are also discussed in this paper.
Anti-hyperlipidemic and hypoglycemic effects of Gynostemma pentaphyllum in the Zucker fatty rat
Gynostemma pentaphyllum is a traditional Chinese medicine used for a variety of conditions, including elevated cholesterol. We have examined the pharmacological anti-hyperlipidemic and hypoglycemic effectiveness of Gynostemma pentaphyllum in the obese Zucker fatty diabetic rat model. After treatment for 4 days Gynostemma pentaphyllum 250 mg/kg reduced Triglyceride (33%), total cholesterol, (13%) and low density lipoprotein cholesterol levels (33%). These effects were dose-dependent and maintained for at least 5 weeks. Chronic treatment for 3-5 weeks also reduced post-prandial hyperTriglyceridemia induced by olive oil 10 mg/kg in the Zucker fatty rats but had no significant effect in lowering sucrose-induced hyperglycemia in Sprague-Dawley rats. A novel regulation by Gynostemma of glucose levels was also observed in the Zucker fatty rat model. In a glucose tolerance test in obese and lean Zucker rats pretreatment with Gynostemma pentaphyllum 250 mg/kg demonstrated glucose levels were significantly less 2 hours post challenge (20%) in the Gynostemma pentaphyllum obese rats compared to the control group. Gynostemma pentaphyllum did not significantly reduce glucose levels at 120 min in the lean strain, in contrast to the 20% decrease seen in the obese rat. In vitro, Gynostemma pentaphyllum inhibited alpha-glucosidase activity (50% inhibition at 42.8), which compared to acarbose (50% at 53.9 microg/mL). The improvement in glucose tolerance at 120 min by Gynostemma pentaphyllum in obese Zucker fatty rats but not lean rats suggests that it may improve insulin receptor sensitivity and together with the significant reduction of hyperTriglyceridemia, cholesterol and low density lipoprotein cholesterol suggests that Gynostemma should be examined further by oral hypoglycemic/anti-hyperlipidemic therapy.
Phytopreventative anti-hyperlipidemic effects of gynostemma pentaphyllum in rats
Results: 1 g/kg P407 induced plasma Triglyceride (25 fold), total cholesterol (6 fold), low density lipoprotein cholesterol (LDL) (7 fold), high density lipoprotein cholesterol (HDL) (1.6 fold), and nitrite (8 fold). After acute (4 days) and chronic (12 days) oral administration the gypenoside extract (250 mg/kg) reduced Triglyceride (53% and 85%, respectively) and total cholesterol levels (10% and 44%, respectively). No significant effects on LDL or HDL cholesterol were observed. The gypenosides reduced nitrite approximately 80%. Similar results were obtained with atorvastatin (75 mg/kg for 4 days); except that LDL cholesterol was reduced (17%) and HDL cholesterol increased. 50% of lipoprotein lipase (LPL) plasma activity was inhibited by approximately 20 microM P407. Gynostemma had no effect on LL, however, it reversed the P407 inhibition of LPL activity in a concentration-dependent manner, with a 2-fold increase at approximately 10 microg/ml.
Conclusions: These studies demonstrate efficacy of Gynostemma pentaphyllum in lowering Triglyceride, cholesterol and nitrite in acute hyperlipidemia. The results suggest further investigations of Gynostemma gypenosides are warranted to examine the mechanisms of this activity.
Hawthorn (Crataegus oxyacantha)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
The use of alcoholic beverages is more common and accepted by our society despite the health risks. Alcohol catabolism produces free radicals that cause oxidative stress and damage in liver principally. Hawthorn (Crataegus oxyacantha) is a medicinal plant that has been shown to have wide variety of polyphenolic compounds with antioxidant and hypolipidemic effect. The objective of this study was the evaluation of Hawthorn methanol extract as preventive treatment in alcoholic damage. A rat model of chronic alcoholic intake was generated with the administration of 3 g/kg/day in two times with 35 % ethanol for twelve weeks to evaluate the protective effect of 50 mg/kg/day for twelve weeks of Hawthorn administration by the determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltranspeptidase (γ-GT), acid phosphatase (ACP), total bilirubin, liver glycogen, lipid peroxidation, serum total antioxidant capacity (TAC), total cholesterol, Triglycerides, low density lipoproteins (LDL), and high density lipoproteins (HDL) levels in blood and hepatic tissues. Oxidative stress was evaluated by lipid peroxidation through MDA and TAC in the serum of animals. Lipid profile and glycogen was measured by LDL, HDL and glycogen concentration, respectively. Histological tissue cuts were visualized by hematoxylin eosin and Masson trichrome staining. Hawthorn treatment decreased AST, ALT, γ-GT and ACP activity in liver damage with a decrease of total bilirubin and an increase of liver glycogen stores in rats administrated with alcohol. Hawthorn showed an antioxidant and preventive effect decreasing liver lipid peroxidation levels and increasing serum TAC evidencing a hypolipidemic effect decreasing total cholesterol, Triglycerides and LDL levels without affecting HDL levels. Our results indicate that Hawthorn exhibited a protective effect against liver damage in rats with chronic alcohol administration providing a possible alternative treatment for alcohol liver damage.
Results and Discussion: The highest number of cases were in the age group 51-55, with maximum incidence in females. Out of 30 cases studies 23 patients shows significant improvement in total cholesterol values, 26 patients shows significant improvement in Triglycerides values, 22 patients shows significant improvement in LDL value, 26 patients shows significant improvement in HDL value. In the present study bad cholesterol levels were found to be decreased along with that there is improvement in good cholesterol values. The wellbeing level of the patient is good after treatment with medicine Crataegus. By using the paired t test, the calculated t value of total cholesterol, Triglycerides, HD Land LDL were found to be greater than the table value ie, p<0.01.Potencies used for this study is 30,3X and mother tincture and mother tincture is effective in43.33%.
Herniaria hirsuta L.
Etnopharmacological relevance
Infusions of Herniaria hirsuta L., Herniaria glabra L. and Herniaria fontanesii J.Gay are well known in Moroccon folk medicine for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic. Herniariae Herba which can contain H. glabra and H. hirsuta is known in Europe as an urological drug.
Aim of the study
To investigate the efficacy of a standardized infusion of Herniaria hirsuta against choleltihiasis, and evaluation of its genotoxicity.
Methods and materials
An analytical HPLC-UV method to quantify flavonoids and saponins present in the extract of H. hirsuta was developed and validated. An in vivo experiment to evaluate thecholesterolloweringeffect of a infusion of H. hirsuta in the gall bladder of dogs was carried out. Dogs were divided into 3 groups i.e. control dogs (CG), dogs treated with ursodeoxycholic acid (UDCA) (2×7.35 mg/kg body weight/day) and dogs treated with the standardized infusion (HG) (2×48.5 mg/kg body weight/day). Dogs were fed a fattydiet during 120 days after which adiet without additional fat was introduced till day 180. Treatment started 30 days after introduction of the fattydiet and lasted till the end of the experiment. A bile andblood sample of each dog was collected every 30 days, after which the concentration ofcholesterol was determined. An Ames test was performed according to the OECD-guidelines.
Results
The validated HPLC-UV method showed a linear calibration model and an acceptable precision for the total flavonoid content (total content 4.51%) as well as the total saponin content (12.74%). The in vivo experiments already showed a minor difference for bilecholesterol between CG and HG after 30 days of treatment with the infusion, and the difference was more pronounced after 90 days of treatment. Even 30 days after discontinuation of thecholesterol-richdiet a significant difference remained between CG and HG. There was no statistically significant difference inbloodcholesterol. The Ames test showed that the infusion of H. hirsuta could be considered as being free from genotoxic risks.
Conclusion
A method for the standardization of a infusion of Herniaria hirsuta was developed and validated. Prolonged use of this standardized H. hirsuta extract resulted in acholesterol-loweringeffect in the bile of dogs. Since this pharmacologicaleffect prevents the formation of gallstones and can contribute to solving existing gallstones, a standardized infusion of H. hirsuta may have a positiveeffect in the treatment of gallstones in human patients.
cholesterollowering effect in the gall bladder of dogs by Herniaria hirsuta
Infusions of Herniaria hirsuta L., H. glabra L. and H. fontanesii J. Gay (Caryophyllaceae) are well known in Moroccon folk medicine for the treatment of biliary dyskinesia, (uro)lithiasis or as a diuretic, and in Europe as an urological drug [1, 2]. An in vivo experiment to evaluate thecholesterolloweringeffect of a decoction of H. hirsuta in the gall bladder of dogs was carried out. Three groups of dogs i.e. control dogs (CG), dogs treated with ursodeoxycholic acid (UDCA) (2 × 7.35 mg/kg body weight/day) and dogs treated with the standardized decoction (HG) (2 × 48.5 mg/kg body weight/day) were fed a fattydiet during 120 days after which adiet without additional fat was introduced till day 180 [3]. Treatment started 30 days after the start of the fattydiet and lasted until the end of the experiment. A bile andblood sample of each dog was collected every 30 days, after which thecholesterol level was determined. The in vivo experiments already showed a minor difference for bilecholesterol between CG and HG after 30 days of treatment with the decoction, and a more pronounced difference after 90 days of treatment. Even 30 days after discontinuation of thecholesterol-richdiet a significant difference remained between CG and HG. There was no significant difference inbloodcholesterol between the groups. Prolonged use of this standardized H. hirsuta extract resulted in acholesterol-loweringeffect in the bile of dogs. Since this pharmacologicaleffect prevents the formation of gallstones and can contribute to solving existing gallstones, a standardized decoction of H. hirsuta may have a positiveeffect in the treatment of gallstones in human patients.
Hesperetin
Evaluation of hesperetin 7-O-lauryl ether aslipid-lowering agent inhigh-cholesterol-fed rats
Thelipid-lowering efficacy of hesperetin was revealed in preliminary studies on experimental animals. As such, the current study compared theeffect of hesperetin 7-O-lauryl ether, with that of hesperetin and lovastatin on thelipid profile andcholesterol-regulating mechanism inhigh-cholesterol-fed rats. Male rats were fed ahigh-cholesteroldiet (1%, wt/wt) orhigh-cholesteroldiet supplemented with lovastatin (1, 0.02%, wt/wt), hesperetin (2, 0.02%, wt/wt), or hesperetin 7-O-lauryl ether (3, 0.031%, wt/wt) for six weeks. The supplemental amount of 3 was 0.066 mmol/100 gdiet as an equivalent to the supplemental amount of 2. The plasma totalcholesterol and Triglyceride levels were significantly lowered by the 2 and 3 supplements compared with the control or 1-supplemented group. The hepatic HMG-CoA reductase activities were also significantly lower in all the supplemented groups compared with the control group, and the hepatic ACAT activity was significantly lower in the 2- and 3-supplemented groups. The supplementation of 3 resulted in ahigher excretion of total neutral sterol and total fecal sterol compared with the control or 1-supplemented group. Accordingly, overall, compound 3, exhibited a more potent plasmalipid-loweringeffect than compound 1 based on inhibitingcholesterol biosynthesis and esterification, while also increasing the fecal sterol excretion.
This study examined thelipid-loweringeffect of hesperetin 7-O-lauryl ether inhigh-cholesterol-fed rats. The supplementation of this compound waseffective in alteringlipidmetabolism andlowering plasmacholesterol level.
Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats
Background: Hesperetin is a naturally occurring flavonoid that has hypolipidemic properties. Methods: Male rats were fed a 1 g/100 g high-cholesterol diet for 5 weeks along with hesperetin (0.02%, 0.066 mmol/100 g diet) and hesperetin metabolites. The hesperetin metabolites, m-hydroxycinnamic acid (m-HC), 3,4-dihydroxyphenylpropionic acid (3,4-DHPP), and 3-methoxy-4-hydroxycinnamic acid (ferulic acid), were supplemented based on an equivalent amount of hesperetin. Results: The supplementation of hesperetin and its metabolites significantly lowered the plasma total cholesterol and Triglyceride concentrations compared to the control group. The hepatic HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the hesperetin and its metabolite supplemented groups than in the control group. The excretion of acidic sterol was significantly higher in the hesperetin, m-HC, 3,4-DHPP, and ferulic acid supplemented groups than in the control group. Conclusions: These results demonstrated that the hesperetin metabolites played as potent a role as hesperetin in plasma lipid-lowering activities in vivo, and further suggest that cholesterol biosynthesis and esterification were concomitantly reduced by hesperetin and its metabolites, as indicated by the decreased HMG-CoA reductase and ACAT activities.
The citrus flavonoids, naringenin and hesperetin, lower plasma cholesterol in vivo. However, the underlying mechanisms are not fully understood. The ability of these flavonoids to modulate apolipoprotein B (apoB) secretion and cellular cholesterol homeostasis was determined in the human hepatoma cell line, HepG2. apoB accumulation in the media decreased in a dose-dependent manner following 24-h incubations with naringenin (up to 82%, P < 0.00001) or hesperetin (up to 74%, P < 0.002). Decreased apoB secretion was associated with reduced cellular cholesteryl ester mass. Cholesterol esterification was decreased, dose-dependently, up to 84% (P < 0.0001) at flavonoid concentrations of 200 μM. Neither flavonoid demonstrated selective inhibition of either form of acyl CoA:cholesterol acyltransferase (ACAT) as determined using CHO cells stably transfected with either ACAT1 or ACAT2. However, in HepG2 cells, ACAT2 mRNA was selectively decreased (−50%, P < 0.001) by both flavonoids, whereas ACAT1 mRNA was unaffected. In addition, naringenin and hesperetin decreased both the activity (−20% to −40%, P < 0.00004) and expression (−30% to −40%, P < 0.02) of microsomal Triglyceride transfer protein (MTP). Both flavonoids caused a 5- to 7-fold increase (P < 0.02) in low density lipoprotein (LDL) receptor mRNA, which resulted in a 1.5- to 2-fold increase in uptake and degradation of 125I-LDL.
The present study investigated whether combined ingestion of green tea catechins (GTC) and monoglucosyl hesperidin (GHES) influences the pharmacokinetic parameters of polyphenols and serum Triglycerides (TG). We conducted 2 randomized, controlled trials. Study 1: 8 healthy male subjects participated in a crossover study in which they ingested a test beverage containing GHES (0, 84, 168, or 336 mg GHES) with GTC, or 336 mg GHES without GTC. After ingestion, the pharmacokinetic changes in plasma hesperetin (HEP) and catechins were measured. Study 2: 36 healthy male and female subjects (mean age, 53 ± 2 years; mean BMI, 25.2 ± 0.5 kg m−2) were recruited for a double-blind, placebo-controlled study in which they ingested a test beverage containing 165 mg GHES with 387 mg GTC or a placebo beverage daily for 4 weeks. Fasting serum TG and other lipids and glucose metabolites were analyzed. Study 1 showed that the pharmacokinetics of HEP did not differ significantly between the 336 mg GHES without GTC treatment and the 168 mg GHES with GTC treatment. Study 2 showed that continuous ingestion of 165 mg GHES and 387 mg GTC for 4 weeks significantly decreased fasting serum TG levels compared with baseline values (change in TG, −30 ± 13 mg dl−1, P = 0.040) in the intention-to-treat analysis. In conclusion, our findings suggest that GTC affects the oral bioavailability of GHES, and combined ingestion of low doses of GHES with GTC effectively improves fasting TG levels.
Holy Basil Extract
During the last week of the experiment, rats’ feces were collected for 3 consecutive days to determine fecal lipids and bile acids excretion. The rats were fasted overnight and anesthetized by intraperitoneal injection with zolitil (40 mg/kgbw) plus xylazine (3 mg/kgbw). Blood was collected from the abdominal vein to determine the serum lipid profile including total cholesterol (TC), Triglyceride, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). The atherogenic index (AI) was later calculated as the ratio of [TC-(HDL-C)]/(HDL-C). The liver and heart were also isolated, cleaned, and weighed. Liver and fecal lipids were extracted by modified method of Folch et al. [13]. Fecal bile acids including cholic acid and deoxycholic acid, the primary fecal bile acids in rat, were extracted and assayed by modified method described by Mosbach et al. [14] and Rizvi et al.
Hordeum vulgare L.extract
Pharmacological and therapeutic potential of Hordeum vulgare
Introduction
One of the first grains to be cultivated was Hordeum vulgare, which was grown in the Fertile Crescent, a region of Western Asia near the Nile River in North-East Africa and many other regions like russia, china. It has a lot of soluble fiber, especially beta-glucans, which help controlblood sugar and lowercholesterol. It is a grain of the Poaceae family and is one of the earliest plants with the greatest significance in Chinese medicine. Traditional Chinese Medicine (TCM) practitioners have used it for treating hyperprolactinemia, obesity etc. Hordeum vulgare is used in the preparation called “Smilax” which is used for weight loss in china. Hordeum vulgare has been used as a poultice to treat burns and wounds because it is thought to be anti-inflammatory, anti-fatigue, diuretic, antioxidant, aphrodisiac, antiviral, antiprotozoal, astringent, demulcent, digestive, expectorant, febrifuge, antimutagenic, and emollient.
Methodology
The online databases including scopus, web of science, Google Scholar, and PubMed, were searched using different keywords: Hordeum vulgare, antinflammatory activity, traditional uses, and antimutagenic activity, Chinese herb, hordeum vulgare. The purpose of this review was therefore to summarize the previously reported phytopharmacological status of the chosen plant species.
Results
The results of our analysis revealed that Hordeum vulgare Linn. containsdietary fiber, vitamins, minerals, and phytochemicals including, flavonoids, saponins, etc. In addition, previous research has demonstrated that plant extracts and isolated principles of Hordeum vulgare also possess significant pharmacological activity including antiviral, anti-inflammatory, febrifuge, anti-mutagenic and others.
Discussion
Hordeum vulgare has a good potential for generating therapeutics for the treatment of inflammation, obesity, cancer and also worked asdietary supplements for minerals and vitamin deficiency, according to the below-mentioned human and animal studies. Also, clinical research has shown that Hordeum vulgare is a safe and efficient herb for human intake and thus should be included indietary intakes and as active constituents in pharmaceutical formulations.
Conclusion
This review will talk about how the plant chemicals in Hordeum vulgare can be used to treat and prevent diseases. This review also helps the researchers to work on the Hordeum vulgare with the focus on bioactivity and toxicity.
Results: Results indicated that barley grass juice (Hordeum vulgare L.) exhibited potent in vitro antioxidant activity. Rats administered with high fat diet for 60 days showed a significant increase in body weight, BMI, altered lipid profile, liver function markers like AST, ALT, ALP and increased expression of PPAR-gamma and caspase 3. However, administration of barley grass juice for 60 days, profoundly decreased the bodyweight, BMI, improved lipid profile and liver function markers. This was supported by the decreased expression of PPAR-gamma and caspase 3 in liver. Histopathological variations observed in liver and carotid artery of high fat diet group, when treated with BJG showed preserved hepatocytes and reduced atherosclerosis. GC-MS analysis identified the presence of 12 phytochemical constituents in barley grass juice.
Hyperoside
Taken together, the results suggest that hyperoside could improve the condition of NAFLD by regulating the cholesterol metabolism as well as BAs metabolism and excretion. These findings contribute to understanding the mechanisms by which hyperoside lowers the cholesterol and Triglyceride in NAFLD rats.
Ilex latifolia
To explore whether holly polyphenols extracts (HPE) could alleviate hepatic injury by regulating anti-oxidative capacity and ferroptosis, the piglets were fed a basal diet with or without HPE, followed by intraperitoneal administration of diquat to trigger liver oxidative stress and damage in this study (21). We reveal that HPE supplementation improves hepatic morphology, enhances hepatic anti-oxidative capacity, and reduces the expression of ferroptosis mediators in diquat-challenged piglets.
Ipomoea batatas (L.) leaves
Objectives
Cardiovascular diseases, especiallyAtherosclerosis, are the leading cause of human mortality in Indonesia. Ipomoea batatas (L.) is a food plant used in Indonesian traditional medicine to treat cardiovascular diseases and related conditions. We assessed theAnti-atherosclerotic activity of the aqueous extract of I. batatas leaves in a rat model ofhigh-fatdiet-inducedAtherosclerosis and its mechanism.
Methods
The presence of amino acid content in the I. batatas L. purple variant was determined by liquid chromatographyhigh-resolution mass spectrometry (LC-HRMS). Thirty male Wistar rats were divided into five groups (n=6/group), i.e., standarddiet group (SD),high-fatdiet group (HF), and HF plus I. batatas L. extracts orally (625; 1,250; or 2,500 mg/kg) groups. The numbers of macrophages and aortic wall thickness were analyzed histologically. Immunohistochemical analyses were performed to assess foam cells-oxidized low-density lipoprotein (oxLDL), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF) expression in the aorta.
Results
LC-HRMS analysis showed nine amino acid content were identified from I. batatas L. In vivo study revealed that oral administration of I. batatas L. leaf extract alleviated foam cells-oxLDL formation and aortic wall thickness caused byhigh-fatdietAtherosclerosis rats. Further, I. batatas L. leaf extract promoted the number of macrophages and modulated VEGF and eNOS expression in the aorta.
Conclusions
I. batatas L. leaf extract shows a positive anti-Atherosclerosiseffect. Furthermore, the mechanism may promote the macrophages, eNOS, VEGF expressions, and inhibition of foam cells-oxLDL formation and aortic wall thickness with the best dosage at 2,500 mg/kg. This could represent a novel approach to prevent cardiovascular diseases.
Hyperglycemia is a condition with high glucose levels that may result in dyslipidemia. In severe cases, this alteration may lead to diabetic retinopathy. Numerous drugs have been approved by officials to treat these conditions, but usage of any synthetic drugs in the long term will result in unavoidable side effects such as kidney failure. Therefore, more emphasis is being placed on natural ingredients due to their bioavailability and absence of side effects. In regards to this claim, promising results have been witnessed in the usage of Ipomoea batatas (I. batatas) in treating the hyperglycemic and dyslipidemic condition. Thus, the aim of this paper is to conduct an overview of the reported effects of I. batatas focusing on in vitro and in vivo trials in reducing high glucose levels and regulating the dyslipidemic condition. A comprehensive literature search was performed using Scopus, Web of Science, Springer Nature, and PubMed databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) Beneficial effect OR healing OR intervention AND (2) sweet potato OR Ipomoea batatas OR traditional herb AND (3) blood glucose OR LDL OR lipid OR cholesterol OR dyslipidemia. Only articles published from 2011 onwards were selected for further analysis. This review includes the (1) method of intervention and the outcome (2) signaling mechanism involved (3) underlying mechanism of action, and the possible side effects observed based on the phytoconstiuents isolated. The comprehensive literature search retrieved a total of 2491 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 23 articles were chosen for further review. The results from these articles indicate that I. batatas has proven to be effective in treating the hyperglycemic condition and is able to regulate dyslipidemia. Therefore, this systematic review summarizes the signaling mechanism, mechanism of action, and phytoconstituents responsible for those activities of I. batatas in treating hyperglycemic based on the in vitro and in vivo study.
Different allopathic drugs are being used for the treatment of diabetes mellitus but more emphasis are being placed on the use of medicinal plants, herbs, and natural extracts of fruits and vegetables due to their easy availability, easy consummation with low cost, and with no well-reported side effects. White skinned sweet potato (WSSP; Ipomoea batatas L.) peel-off was selected to find out its antidiabetic potential as well as to explore the effects on selected biochemical parameters in diabetes-induced Wistar rats. In young (3–4 months) and old (up to 1 year) diabetic Wistar rats, it was found that WSSP (I. batatas L.) peel-off significantly (P < 0.05) decreased blood glucose level, protein glycation level, total cholesterol, Triglycerides, and low-density lipoprotein (LDL)-cholesterol. A significant (P < 0.05) increase in high-density lipoprotein (HDL)-cholesterol level after treatment was also reported. Furthermore, it was also found that WSSP peel-off also had beneficial effects on total protein concentration, albumin, globulin, and liver enzymes (serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). It might be concluded that antidiabetic potential of WSSP extract is due to the presence of bioactive compounds like glycoprotein, anthocyanins, alkaloids, and flavonoids, which act as insulin-like molecules or insulin secretagogues constituents in sweet potatoes peel-off and these antidiabetic proteins were extracted out in more concentration in methanol due to its organic nature. Further research is needed to purify and quantify the antidiabetic components responsible for antidiabetic effects of WSSP and it should be available in compact dose form for the treatment of diabetic patients.
Results: The statistics were assessed by using one way ANOVA followed by Dunnet’s multiple comparison tests. To unfold the mechanism we studied all the biochemical parameters like Total cholesterol (TC), Triglycerides (TG), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and histopathological examination of Liver tissue section. The ethanolic extracts of seeds of Canavalia ensiformis showed significant reduce of the level of cholesterol, Triglycerides, LDL, VLDL and a significant increase in the serum level of HDL at 400 mg/kg rather than 200 mg/kg.
Conclusion: Further the characterization and isolation of the constituents could be done to know the exact mechanism of hyperlipidemic activity. Statistical analysis of this screening method conforms that the proposed method is appropriate and it can be useful, gives the basic idea to the researcher who is working in an area like Antihyperlipidemic activity.
Jackbean (Canavalia ensiformis) seed protein
cholesterol lowering effect of jackbean (Canavalia ensiformis) seed protein.
1. Feeding jackbean (Canavalia ensiformis) protein to hypercholesterolemic rats considerably loweredcholesterol levels in the experimental animals than when the animals were fed casein (control)diets. 2. Thecholesterol levels in various components of test animals fed the Canavaliadiet ranged from 53.3 +/- 1.7 to 74.8 +/- 3.4 mg/g (plasma); from 11.1 +/- 7.4 to 23.3 +/- 5.4 mg/g (liver); from 7.1 +/- 0.7 to 9.3 +/- 1.7 mg/g (kidney) and 1.9 +/- 0.3 to 3.2 +/- 0.6 mg/g (heart). 3. Totallipid levels estimated for the animals on the testdiets ranged from 80.0 +/- 2.4 to 130.1 +/- 9.1 mg/g (plasma); from 19.1 +/- 3.4 to 28.5 +/- 1.1 mg/g (liver); from 17.0 +/- 4.1 to 23.0 +/- 6.0 mg/g (kidney) and from 13.2 +/- 4.0 to 18.0 +/- 2.5 mg/g (heart). 4. Total protein levels in plasma of experimental animals were not significantly different (P less than 0.05) after feeding the control or testdiets.
Kelp extract
In this meta-analysis, we found that brown seaweed intake significantly decreased the levels of total cholesterol (mean difference (MD): −3.001; 95% CI: −5.770, −0.232) and low-density lipoprotein (LDL) cholesterol (MD: −6.519; 95% CI: −12.884, −0.154); nevertheless, the statistically significant association of brown seaweed intake with high-density lipoprotein (HDL) cholesterol and Triglycerides were not observed in our study (MD: 0.889; 95% CI: −0.558, 2.335 and MD: 8.515; 95% CI: −19.354, 36.383). Our study demonstrated that brown seaweed and its extracts decreased total cholesterol and LDL cholesterol levels. The use of brown seaweeds may be a promising strategy to reduce the risk of dyslipidemia. Future studies involving a larger population are warranted to investigate the dose–response association of brown seaweed consumption with dyslipidemia.
Kenaf (Hibiscus cannabinus L., Malvaceae)
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Results: All the kenaf samples exhibited to contain most of the major phytochemicals. KSE possessed gallic acid, tannic acid, catechin, benzaldehyde, benzoic acid, syringic acid, sinapic acid, ferulic acid, naringin acid, and protocatechuic acid. The significant higher (P<0.05) serum total cholesterol, low density lipoprotein cholesterol and MDA levels in HD group without treatment than the normal control group suggested the hypercholesterolemia was induced by the incorporation of cholesterol into diet. KSE exhibited higher cholesterol-lowering properties due to the significant lower (P<0.05) in serum Triglycerides, total cholesterol and MDA levels. KSE showed the highest efficiency of cholesterol-lowering activity, followed by KSO, MKSO and DKSM.
Kepuh (Sterculia foetida) Leaves
Cardiovascular disease causes thehighest mortality rate in the world. Atherosclerotic plaque is the most common etiology of cardiovascular disease.high levels ofcholesterol in circulation is the pathophysiology ofAtherosclerosis formation.Atherosclerosis risk can be lowered to 20-40% with statins. Statins areeffective inlowering total andLDLcholesterol, but these drugs have been reported to cause sideeffects. Therefore, it needed an alternative medicine to prevent the process ofAtherosclerosis using kepuh leaves (Sterculia foetida). Flavonoids contained in Kepuh leaves improvelipid profiles. The aims of this study is to prove theeffectiveness of Sterculia foetida inloweringcholesterol, Triglyceride and reduce the amount of foam cells onhigh-fat-diet induced rats. The research design is quasi-experimental with post test only design. Animals are grouped into normal group, negative control group and three treatment groups that were given kepuh leaves extract at the dose of 200 mg/kgBB, 400 mg/kgBB, and 800 mg/ kgBB. Rats were givenhigh-fatdiet of initial intravenous adrenaline injection 0.006 mg/200 gBB and duck egg yolks 5 g/kgBB for 21 days.cholesterol and Triglycerides were measured by enzymatic methods and aortic tissue stained with HE. ESf reducecholesterol significantly and reduce the amount of foam cells on aorta.
A Review on Sterculia foetida Linn.
Sterculia foetida Linn., (Sterculiaceae) known as Wild Almond or Java olive is an attractive umbrella shaped spreading tree. Traditionally, leaves as well as the seeds have important medicinal values as they contain Sterculic acid(53%) as a constituent which has proven to have interesting pharmacological applications such as anti-inflammatory, anti-diabetic and anti-obesity potentials. The tree yield edible seeds rich in fat (30–36%) and protein 11.4%. Traditionally leaves and bark are used as aperient, diaphoretic, diuretic and also used in the treatment of rheumatism, obesity, gonorrhoea, dropsy, skin diseases etc,. The plant is rich in fatty acids and flavonoids. This review summarizes the overall research of phytochemical and pharmacological activities of Sterculia foetida in the recent years.
L‐carnitine
l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes
Background
Patients with type 2 diabetes are underhigh oxidative stress, and levels of hyperglycemia correlate strongly with levels ofLDL oxidation. Carnitine favorably modulates oxidative stress.
Objective
This objective of this study was to evaluate the efficacy of l-carnitine on the reduction ofoxidizedLDLcholesterol in patients with type 2 diabetes.
Design
Eighty-one patients with diabetes were randomly assigned to 1 of 2 treatment groups for 3 mo. The 2 groups received either 2 g l-carnitine once daily (n = 41) or placebo (n = 40). The following variables were assessed at baseline, after washout, and at 1, 2, and 3 mo of treatment: body mass index, fasting plasmaglucose, glycosylated hemoglobin, totalcholesterol,LDLcholesterol, HDLcholesterol, Triglycerides ,apolipoprotein A1,apolipoprotein B-100,oxidizedLDLcholesterol, thiobarbituric acid–reactive substances, and conjugated dienes.
Results
At the end of the study period, the l-carnitine-treated patients showed significant improvements compared with the placebo group in the following markers:oxidizedLDL levels decreased by 15.1 compared with 3.0 U/L (P < 0.001);LDLcholesterol decreased by 0.45 compared with 0.16 mmol/L (P < 0.05); Triglycerides decreased by 1.02 compared with 0.09 mmol/L (P < 0.001);apolipoprotein A1 concentrations decreased by 0.12 compared with 0.03 mg/dL (P < 0.05);apolipoprotein B-100 concentrations decreased by 0.13 compared with 0.04 mg/dL (P < 0.05); thiobarbituric acid–reactive substance concentrations decreased by 1.92 compared with 0.05 (P < 0.001), and conjugated diene concentrations decreased by 0.72 compared with 0.11 in the placebo group (P < 0.001).
Conclusion
Our study indicates that oral administration of l-carnitine reducesoxidizedLDLcholesterol levels in patients with type 2 diabetes.
effects of L-carnitine supplementation onlipid profiles in patients with coronary artery disease
Background
L-carnitine (LC) plays an important physiologic role inlipidmetabolism. To date, no clinical study has been performed to examine theeffect of LC supplementation on thelipid status of coronary artery disease (CAD) patients. The aim of this study was to investigate thelipidloweringeffects of LC supplementation (1000 mg/d) in CAD patients.
Methods
CAD patients were identified by cardiac catheterization as having at least 50 % stenosis of one major coronary artery. Forty-seven subjects were recruited and randomly assigned to the placebo (n = 24) and to the LC (n = 23) groups. The intervention was administered for 12 weeks. The levels of LC,lipid profiles, and antioxidant enzyme activity (superoxide dismutase, SOD) were measured.
Results
The subjects in the LC group had significantlyhigher SOD activity (20.7 ± 4.2 versus 13.1 ± 2.9 U/mg of protein, P < 0.01),high density lipoprotein-cholesterol (1.34 ± 0.42 vs. 1.16 ± 0.24 mmol/L, HDL-C, P = 0.03), andapolipoprotein-A1 (Apo-A1, 1.24 ± 0.18 vs. 1.12 ± 0.13 g/L, P = 0.02) than those in the placebo group at week 12. Triglyceride (TG) level was slightly significantly reduced (1.40 ± 0.74 vs. 1.35 ± 0.62 mmol/L, P = 0.06) and the level of LC was negatively correlated with Triglyceride andapolipoprotein-B (Apo-B), and positively correlated with HDL-C and Apo-A1 after LC supplementation. Additionally, SOD activity was significantly negatively correlated withlipid profiles (totalcholesterol, TG, and Apo-B) after supplementation.
Conclusion
LC supplementation at a dose of 1000 mg/d showed significantly increased in HDL-C and Apo-A1 levels and a slight decrease in Triglyceride levels but no other changes in otherlipids in CAD patients, and thislipid-loweringeffect may be related to its antioxidant ability. Further studies should be conducted to define an optimal dose of LC forlipid-lowering in patients with CAD.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Results:
Hepatic Triglycerides and the different forms of carnitine showed no difference between sampling periods (p>0.05). Hepatic Triglycerides concentration was low and decreased in response to 200 g/d L-carnitine fumarate supplementation (p<0.05). This decrease in hepatic Triglycerides could be due to increased fatty acid oxidation. L-carnitine supplementation significantly increased (p<0.05) blood urea concentration, possibly through stimulation of the urea cycle, as previously described in other species.
Conclusion:
Supplementation with L-carnitine decreased the hepatic concentration of Triglycerides, possibly due to increased liver oxidation of fatty acids.
Results: Out of 3460 potential papers selected based on keywords search, 67 studies met the inclusion criteria and were eligible for the meta-analysis. The pooled results indicated that L-carnitine administration led to a significant decrease in Triglycerides (WMD: -10.35; 95% CI: -16.43, -4.27), total cholesterol (WMD: -9.47; 95% CI: – 13.23, -5.70) and LDL-cholesterol (LDL-C) concentrations (WMD: -6.25; 95% CI: -9.30, -3.21), and a significant increase in HDL-cholesterol (HDL-C) levels (WMD: 1.39; 95% CI: 0.21, 2.57). L-carnitine supplementation did not influence VLDL-cholesterol concentrations. When we stratified studies for the predefined factors such as dosage, and age, no significant effects of the intervention on Triglycerides, LDL-C, and HDL-C levels were found.
Conclusion: This meta-analysis demonstrated that L-carnitine administration significantly reduced Triglycerides, total cholesterol and LDL-cholesterol levels, and significantly increased HDL-cholesterol levels in the pooled analyses, but did not affect VLDL-cholesterol levels; however, these findings were not confirmed in our subgroup analyses by participant’s health conditions, age, dosage of L-carnitine, duration of study, sample size, and study location.
Lablab purpureus (Linn.) Sweet extract
Lablab purpureus (L) bean is an undervalued or underutilized orphan crop in many tropical countries, where different forms of malnutrition are associated with stunting growth and cognitive deficiencies. We previously reported that L. purpureus contains ω-3 α-linolenic acid (ALA, C18:3, ω-3), which can act as the precursor of ω-3 docosahexaenoic acid (DHA, C22:6, ω-3). Inadequate level of DHA impairs growth, development, and cognitive performance. Therefore, we evaluated if supplementation of L. purpureus seed flour (LPS) affects the nutritional status, in terms of body weight gain, plasma proteins, and DHA levels of malnourished model rats. Three groups of rats, namely, controls, malnourished alone (MN), and 15% LPS-supplemented malnourished (MN + LPS) rats were fed with LPS for 12 weeks. Afterward, body weight, liver weight, brain weight, plasma proteins, micronutrients,lipid profile, and fatty acid profile of plasma, liver, and brains were determined by standard methods. The levels of liverlipid peroxide (LPO) and proinflammatory TNFα were also measured. The body weight, liver weight,serum total proteins and micronutrients (iron/potassium), and the levels of docosahexaenoic acid significantly increased in the plasma, liver, and brain of MN + LPS rats. Moreover, LPO and TNFα levels reduced significantly in MN + LPS rats. in vitro analysis revealed a significant free radical scavenging and antioxidative potential of L. purpureus seed extract. Thus, L. purpureus not only replenishes protein-energy malnutrition, but also increases the levels of DHA, an indispensable polyunsaturated fatty acid for brain cognition. Finally, our results suggest that L. purpureus might benefit human malnutrition and related cognitive deficits.
Dolichos lablab Protects Against Nonalcoholic Fatty Liver Disease in Mice Fed high-Fat diets
Hyacinth bean, Dolichos lablab or Lablab purpureus, has been used for centuries in India and China as an edible pod and animal forage, as well as to treat diarrhea and other gastrointestinal disease in traditional Korean medicine. Recently, we have demonstrated that D. lablab extract (DLL-Ex) prevented free fatty acid-inducedlipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we, thus, aimed at clarifying the hepatoprotectiveeffects of DLL-Ex in ahigh-fatdiet-induced in vivo animal NAFLD model, as well as at elucidating underlying mechanisms of identifiedeffects. Sixty, 6-week-old, male C57BL/6J mice were randomly divided into six groups: a control group fed a low-fatdiet, fourhigh-fatdiet (HFD) groups, three receiving daily oral supplementation of DLL-Ex (25, 50, and 100 mg/kg/day), and one HFD group receiving daily oral supplementation of MILK (100 mg/kg/day).effects of DLL-Ex supplementation were evaluated by histopathological and histochemical assessments. DLL-Ex supplementation inhibited HFD-induced increases in body weight and body fat mass andameliorated increases in body weight, manifested as decreased liver function tests, lowerserum Triglycerides andcholesterol levels, and increasedserum adiponectin levels. The expression of hepatic genes involved inlipid droplet accumulation and in fatty acid uptake was also decreased. We provide evidence of a protectiveeffect of DLL-Ex against HFD-induced fatty liver disease in an animal model.
The pharmacology and medical importance of Dolichos lablab (Lablab purpureus)-A review
The phytochemical analysis of Dolichos lablab showed that it contained sugar, alcohols, phenols, steroids, essential oils, alkaloids, tannins, flavonoids, saponins, coumarins, terpenoids, pigments, glycosides, anthnanoids, wide range of minerals and many other metabolites. The preliminary pharmacological studies revealed that Dolichos lablab possessed antidiabetic, antiinflammatory, analgesic, antioxidant, cytotoxic, hypolipidemic, antimicrobial, insecticidal, hepatoprotective, antilithiatic, antispasmodic effects and also used for the treatment of iron deficiency anemia. The current review discussed the chemical constituents and pharmacological activities of Dolichos lablab.
Lablab purpureus were more potent at reducing raised serum cholesterol levels than that of Phaseolus angularis (Chau et al. 1998). Both significantly reduced levels of Triglyceride
Lecithin
Elevated plasma lipid concentrations and increased platelet activation are risk factors in the development of atherosclerosis. Nine patients with type IIa hyperlipoproteinemia and nine patients with type IV hyperlipoproteinemia were given soya lecithin, 12 g/day, for 3 months. Plasma cholesterol and Triglycerides were reduced by 15 and 23%, respectively, and HDL-cholesterol increased by 16% in the hypercholesterolemic patients. Platelet function was unchanged. In the hyperTriglyceridemic patients, total cholesterol fell by 18%, Triglycerides by 36%, and HDL-cholesterol increased by 14%. There was a 27% reduction in platelet aggregation (P less than 0.01). Seventeen hyperTriglyceridemic patients then received increasing doses of soya lecithin for 1-month periods (6, 12, and 18 g/day). The optimal lipoprotein-lowering effect was achieved with a daily dose of 12 g soya lecithin per day. Both low-density lipoprotein and very-low-density lipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein A-I concentrations were increased. Platelet aggregation in response to collagen and ADP was significantly reduced, parallel with the reduction in Triglyceride level. Soya lecithin supplementing the diet may be useful in the management of the hyperTriglyceridemic patient.
Leonurine Herba Leonuri (Leonurus artemisia)
Background/aims: Previous studies have demonstrated that leonurine, a unique alkaloid compound of Herba leonuri, can exert anti-oxidative and anti-inflammatoryeffects on the development ofAtherosclerosis (AS). This study was designed to investigate theeffects of leonurine oncholesterolefflux from THP-1 macrophage-derived foam cells and development of atherosclerotic lesions in apoE-/- mice, and further determine the potential mechanisms.
Methods: Human THP-1 cells were fully differentiated into foam cells by the pre-treatment with phorbol-12-myristate-13-acetate (PMA) andoxidized density lipoproteins (ox-LDL). After cells were incubated with various concentrations of leonurine, Oil Red O staining andhigh-performance liquid chromatography (HPLC) assays were utilized to detect cellularlipid accumulation andcholesterol content, respectively. Cellularcholesterolefflux was determined by liquid scintillation counting. The mRNA and protein levels of ATP-binding cassettetransporter A1/G1 (ABCA1/G1), peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) in foam cells were assessed using real-time quantitative PCR (RT-qPCR) and western blot analyses, respectively. Plasma Triglyceride (TG), totalcholesterol (TC),high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels in apoE-/- mice were evaluated using enzymatic methods. The atherosclerotic lesion sizes and collagen contents in aortic roots were determined by Oil Red O and Masson’s trichrome staining, respectively.
Results: Oil Red O staining and liquid scintillation counting assays showed that leonurine significantly inhibitedlipid accumulation and promoted 3H-cholesterolefflux in human THP-1 macrophage-derived foam cells in a concentration-dependent manner. Besides, both the mRNA and protein levels of ABCA1/G1, PPARγ and LXRα were enhanced by leonurine, which were attenuated by LXRα siRNA or PPARγ siRNA transfection. Finally, leonurineimproved plasmalipid profile, decreased atherosclerotic lesion sizes, increased collagen contents and amplified PPARγ, LXRα and ABCA1/G1 expressions in aortic roots of apoE-/- mice.
Conclusions: Leonurine can promotecholesterolefflux and alleviate cellularlipid accumulation by magnifying the expression of ABCA1/G1 in a PPARγ/LXRα signaling pathway-dependent manner in human THP-1 macrophage-derived foam cells and abate atherogenesis in apoE-/- mice, which may offer a promising therapeutic intervention of leonurine in protecting against AS.
Leonurus japonicus Houtt extract
Background: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women’s diseases related to reproductive system. They may attenuate the deterioration of energy,lipid,glucose and bonemetabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored.
Methods: Ovariectomized (OVX) rats were divided into five groups and fedhigh-fatdiets supplemented with 2 % dextrin (control), 2 % APP, 2 % APP + LJH (15:5), APP + LJH + GJE (10:5:5) or 17β-estradiol (30 μg/kg bw/day) for 8 weeks. After 8 weeks of their consumption, energy,lipid,glucose and bonemetabolisms were investigated and hepatic insulin signaling and fatty acidmetabolism were determined.
Results: APP + LJH + GJE, but not APP itself,improved energymetabolism and attenuated a decrease in energy expenditure by the same amount as estrogen. Moreover, APP + LJH + GJE reduced visceral fat and intramuscular fat and increased lean body mass measured by DEXA by as much as the positive-control. APP itself suppressed increasedLDLcholesterol and Triglyceride levels in OVX rats and APP + LJH + GJE alleviated dyslipidemia in OVX rats. Overnight-fastedserum insulin levels and HOMA-IR were reduced in the descending order of APP, APP + LJH, APP + LJH + GJE, positive-control in OVX rats. APP and APP + LJH elevated insulin secretion in the 1st part of OGTT to decreaseserumglucose levels while APP + LJH + GJE reducedserumglucose levels without increasingserum insulin levels during OGTT. APP + LJH + GJE decreased insulin resistance during ITT in OVX rats more than the positive-control. The APP + LJH + GJE group exhibited increased hepatic peroxisomal proliferator-activated receptor-γ coactivator-1α expression, which increased the number of genes involved in fatty acid oxidation and decreased fatty acid synthesis. Hepatic insulin signaling (pAkt and pGSK-1β) was also potentiated to reduce phosphoenolpyruvate carboxykinase proteins.
Conclusion: The combination of APP + LJH + GJE attenuated various menopausal symptoms in OVX rats. Thus, it may have potential as a therapeutic agent for the treatment of postmenopausal symptoms.
We investigated the effects of a Leonurus japonicus ethanol extract (LJE) on nonalcoholic fatty liver disease (NAFLD). An in vitro model of hepatic steatosis was treated with 1 mM free fatty acid (FFA) in HepG2 cells. An in vivo NAFLD model was established using C57BL/6 mice fed a high-fat diet (HFD) and administered LJE (100 or 200 mg/kg) orally for 14 weeks. LJE treatment suppressed lipid accumulation and intracellular Triglyceride levels significantly in a concentration-dependent manner in HepG2 cells. Moreover, LJE significantly reduced the expression of sterol regulatory element binding protein 1-c, and its downstream genes, which are associated with lipogenesis, in HepG2 cells. In HFD-fed mice, LJE treatment decreased body weight significantly and decreased serum alanine transaminase levels to normal values, concurrent with a decrease in hepatic lipid accumulation. Furthermore, LJE supplementation ameliorated insulin sensitivity by decreasing serum glucose and insulin levels. LJE improved hepatic steatosis by increasing the expression of phosphorylated AMP-activated protein kinase and peroxisome proliferator-activated receptor-α in HFD-fed mice and FFA-treated HepG2 cells. The results suggested that LJE might be a potential therapeutic agent to treat NAFLD.
Leptadenia pyrotechnica extract
The aim of the present study was to evaluate thehypolipidemic andAntiatherosclerotic efficacy of methanolic extract of the aerial part of L. pyrotechnica incholesterol fed rabbits. Male rabbits were randomly assigned to three groups: Groups I normal control; Group IIcholesterol (500 mg / kg b. wt. / day) with coconut oil (5 ml/rabbit / day) and Group III ,cholesterol + L. pyrotechnica extract (250 mg / kg b. wt./ day) orally. The whole study lasted for 60 days.
The aim of the present study was to evaluate the hypolipidemic and antiatherosclerotic efficacy of methanolic extract of the aerial part of L. pyrotechnica in cholesterol fed rabbits. Male rabbits were randomly assigned to three groups: Groups I normal control; Group II cholesterol (500 mg / kg b. wt. / day) with coconut oil (5 ml/rabbit / day) and Group III , cholesterol + L. pyrotechnica extract (250 mg / kg b. wt./ day) orally. The whole study lasted for 60 days. Administration of cholesterol caused a significant rise (p<0.001) in the serum levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, Triglycerides and total cholesterol, : HDL-cholesterol and LDL-cholesterol : HDL-cholesterol ratios. Simultaneous administration of L. pyrotechnica extract significantly (p<0.001) prevented the rise in serum total cholesterol, LDL-cholesterol, VLDL-cholesterol, Triglycerides and atherogenic index Hepatic and aortic total cholesterol, Triglycerides, and lipid peroxidation (TBARs) were also lowered significantly in the extract treated rabbits. The Plant extracts also significantly prevented the atheromatic changes and plaque formation in the aorta and favoured increased fecal cholesterol output. Thus, the results indicate hypolipidemic and antiatherosclerotic effect of methanolic extract of L. pyrotechnica.
The administration of L. pyrotechnica (250 mg/kg body weight per day orally) extract significantly (p˂0.001) prevented the rise in serum total cholesterol, LDL-cholesterol, VLDL-cholesterol, Triglycerides and atherogenic index. Hepatic and aortic total cholesterol, Triglycerides and lipid peroxidation were also lowered significantly in the extract treated rabbits.
Licorice extract
OBJECTIVE: We previously demonstrated the beneficialeffects ofdietary flavonoids derived from the ethanolic extract of licorice root against atherosclerotic lesion development in association with inhibition of low-density lipoprotein (LDL) oxidation in atherosclerotic mice. Administration of licorice extract to normolipidemic subjects also inhibitedLDL oxidation. In the present study, we extended our investigation to analyze the antiatherogeniceffects of licorice-root extract consumption in moderately hypercholesterolemic patients.
METHODS: Supplementation of licorice root extract (0.1 g/d) to patients for 1 mo was followed by an additional 1 mo of placebo consumption.
RESULTS: Licorice consumption 1) reduced patients’ plasma susceptibility to oxidation (by 19%); 2) increased resistance of plasmaLDL against three major atherogenic modifications: oxidation (by 55%), aggregation (by 28%), and retention, estimated as chondroitin sulfate binding ability (by 25%); 3) reduced plasmacholesterol levels (by 5%), which was due to a 9% reduction in plasmaLDLcholesterol levels; and 4) reduced (by 14%) plasma triacylglycerol levels. After the 1 mo of placebo consumption, these parametersreversed toward baseline levels. Licorice extract supplementation also reduced systolicblood pressure by 10%, which was sustained during the placebo consumption.
CONCLUSIONS:dietary consumption of licorice-root extract by hypercholesterolemic patients may act as a moderatehypocholesterolemic nutrient and a potent antioxidant agent and, hence against cardiovascular disease.
Linum usitatissmum L.seed extract
Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decreaselipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles oflipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventionallipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly—in addition to their normal lipoprotein apheresis regimen—a 10-weekdietary supplementation with flaxseed (28 g/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo.blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was thelipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in totalcholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0–18.8) and 7.3% (4.4–26.6), forcholesterol (p = 0.015) andLDL-C (p = 0.003), respectively. On the other hand, there was no significanteffect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce acholesterol- andLDL-loweringeffect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to controlcholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.
Lonicera japonica Thunb.extract
This study investigated theeffects of honeysuckle extract (Lonicera japonica, HE) on the growth performance andlipidmetabolism of juvenile grass carp (Ctenopharyngodon idella). HE at doses of 10 g kg-1 (LHE), 20 g kg-1 (MHE), and 40 g kg-1 (HHE) were individually mixed with the basaldiet and fed to grass carp for 10 weeks, and ginseng extract (20 g kg-1, GSE) was used as a positive control. The results showed that HE administration exerted noeffect on growth performance, but the hepatosomatic index (HSI) and muscle and liverlipid contents were significantly decreased in the LHE and MHE groups. Theserum levels ofLDL-c, total Triglyceride (TG) and totalcholesterol (TC) also declined in the HE-treated groups. Moreover, the disordered vacuolization and nucleus migration in the liver were alleviated in the MHE and HHE groups, and mRNA expressions of lipogenesis-related genes, such as acc1, fas, srebp1, and pparγ decreased. Similarly, the expression of genes related to lipolysis, such as cpt1, aTGl, lpl, and pparα, was found to be significantly increased in the MHE and HHE groups compared with the control. Taken together, HE caneffectively improve thelipidmetabolism andameliorate thelipid deposition of grass carp and thus may be a promising feed additive in aquaculture.
The levels of total cholesterol (TC), Triglyceride (TG), low-density lipoprotein-cholesterin (LDL-C) and very-low-density lipoprotein-cholesterin (VLDL-C) were significantly descended, while high-density lipoprotein-cholesterin (HDL-C) was significantly ascended (p < 0.01 or p < 0.05). In addition, the oxidant stress in liver was restored as well. The results suggested that LJP could be considered as an ingredient of functional foods for diabetes, and this is the first report about the hypoglycemic and hypolipidemic effects of the polysaccharides extracted from Lonicera japonica.
lupin protein isolate (Lupinus albus)
cholesterol-loweringeffect of whole lupin (Lupinus albus) seed and its protein isolate
This study describes the hypocholesterolaemiceffect of whole lupin and its protein in hamsters. Thediets were: casein (control group HC), lupin protein isolate (group HPI) and whole lupin seed (group HWS).diets from HPI and HWS promoted a significant reduction of totalcholesterol and non-HDLcholesterol in the hamsters’ plasma as compared with HC. The true digestibility of HPI and HC groups were similar and differed significantly from the HWS one, which in turn showed a significant difference in total sterol excretion as compared to the former groups. Histological analysis of the liver revealed that animals fed on HPI and HWSdiets presented a low level of steatosis (level 1) as compared to the ones fed on HCdiet (level 4). Our findings demonstrate that protein isolate from Lupinus albus from Brazil has a metaboliceffect on endogenouscholesterolmetabolism and a protectoreffect on development of hepatic steatosis.
cholesterol-lowering effects ofdietary Lupin (Lupinus albus var Multolupa) in Chickendiets
The present study was undertaken to investigate theeffect of different concentrations of lupin seeds (0, 200, and 400 g/kg), with and withoutcholesterol added (10 g/kg), in chickendiets on performance, relative liver weight, liver fat, intestinal pH and viscosity, and differentbloodserum parameters (glucose,cholesterol, Triglycerides , total biliary salts, amylase, total protein and albumin, and globulin fractions). Increasing the lupin content in thediet reduced weight gain and feed consumption and increased feed-to-gain ratio. A decrease in liver fat, cecal pH,serumglucose,cholesterol, total biliary salts, and total protein and an increase in jejunum viscosity were observed with increasing concentration of lupins.serum albumin, β-globulin, γ-globulin, and albumin:globulin ratio were reduced by the addition of lupin in thediet.cholesterol supplementation ofdiets had noeffect on the performance, cecal pH, andserum Triglycerides . Relative liver weight, liver fat, jejunum viscosity,serumcholesterol, total biliary salts, and total protein were increased, andserumglucose was reduced by addition ofcholesterol.cholesterol increasedserum albumin, α-1 globulin, α-2 globulin, and β-globulin and reduced albumin:globulin ratio and amylase. These results indicate that inclusion of lupin seed in chickendiets causes a growth depression and a reduction ofserumcholesterol andglucose and modifies other physiological parameters.
Lupinus albus administration for 12 weeks resulted in a substantial decrease in serum total and LDL cholesterol and Triglyceride
Lupin protein hydrolyzate decreased plasmatic glucose and Triglycerides. Lupin protein hydrolyzate decreased liver content of cholesterol and Triglycerides.
The aqueous extract of Lupinus albus or Medicago sativa (seeds) or by their mixture has hypoglycemic and hypolipidemic effects by increasing insulin level and decreasing insulin resistance. In addition, they ameliorate most complications of diabetes.
Lupinus angustifolius L.
The present study was undertaken to investigate theeffect ofcholesterol-enriched casein (CAS) and blue lupin seed (BL)diets on thecholesterolmetabolism of intact (INT) and ileorectal anastomosed (IRA) pigs. For 3 weeks, four groups of six pigs were allocated to the treatments (CAS-INT, CAS-IRA, BL-INT, and BL-IRA).diet-induced hypercholesterolemia was inhibited by the BL through a substantial decrease in plasmaLDL-cholesterol. The BL also reduced liver esterified and totalcholesterol, increased hepaticLDL receptor synthesis and HMG-CoA reductase activity, and stimulated intestinal bile acid reabsorption. The neutral sterol output washigher in BL- than in CAS-fed pigs. The bile acid output was lower in IRA than in INT pigs. Surgery also prevented steroid microbial transformation, but it did not influence plasmacholesterol levels.
These results suggest that thehypocholesterolemiceffect of the BL, compared with the CAS, is attributable to impaired intestinalcholesterolabsorption, probably involving increased bile acid reabsorption andhigher contents ofdietary phytosterols, both factors that reduce the micellar solubilization ofcholesterol. Furthermore, according to our data, the contribution of the large intestine tocholesterolmetabolism is very weak.
lutein
We developed a nano-emulsion of lutein disolved in medium chain Triglyceride (MCT) oil with d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) as the surfactant. The average particle size was 223.6 nm, with a polidispersity index (PDI) of 0.5 and a zeta (ζ) potential of −17 mV. Then the efficacy of this nano emulsion was compared to regular lutein in preventingcholesterol induced liver injury in guinea pigs. Twenty-four animals fed a hypercholesterolemicdiet (0.025%cholesterol) were randomly assigned to either one of three groups: control, lutein (3mg/day of regular lutein) or nano (3mg/day lutein as nano-emulsion). After 6 weeks the guinea pigs were sacrificed and their tissues were collected for analyses. As we hypothesized there was significantly more lutein in the tissues and plasma of the animals receiving the nano-emulsion when compared to the other treatments (liver p< 0.001, plasma p< 0.001, adipose (P< 0.001) and eyes (p< 0.001) indicating a greater bioavailability of this carotenoid when a nano-delivery system is used. In terms of liver health, the nano group showed reduced hepatic steatosis scores (P<0.05) and reduced hepatic total and esterifiedcholesterol accumulation (P<0.05). Alanine amino transferase (ALT), a marker for liver damage was also reduced in the nano group (P<0.05).oxidizedLDL in plasma, a marker of oxidative stress andAtherosclerosis risk, was lower in the nano group (2.8±1.0) when compared to the control group (7.9±2.1) (P<0.05) and hepatic OxLDL was lower in both lutein and nano groups when compared to controls: 9.2 ± 4.3 ng/mL, 12.3 ± 4.3 ng/mL and 21.7 ± 14.4 ng/mL, respectively (P<0.05). Results indicate that giving lutein as a nano-formulation increases this compound’s bioavailability and thishigher lutein concentration provides greater protection againstcholesterol-induced hepatic steatosis and oxidative stress than regular lutein.
HFD-induced elevation in the hepatic Triglycerides and cholesterol levels were significantly blocked by lutein.
Lycium barbarum polysaccharides
Bioactive compounds provide new insights into the prevention and treatment of obesity. Lycium barbarum polysaccharide (LBP), a biological macromolecule extracted from Goji berry, has displayed potential for regulating lipid metabolism. However, the relationship between gut microbiota regulation and lipid metabolism is not entirely clear. In the present study, 50, 100, and 150 mg/kg LBP were intragastrically administered to C57BL/6J male mice fed with a high-fat diet simultaneously lasting for twelve weeks. The results showed that 150 mg/kg LBP showed significant results and all doses of LBP feeding (50, 100, 150 mg/kg) remarkably decreased both serum and liver total cholesterol (TC) and Triglyceride (TG) levels. Treatment of 150 mg/kg LBP seems to be more effective in weight loss, lowering free fatty acid (FFA) levels in serum and liver tissues of mice. LBP feeding increased the gene expression of adiponectin and decreased the gene expression of peroxisome proliferator-activated receptor γ, Cluster of Differentiation 36, acetyl-coA carboxylase, and fatty acid synthase in a dose-dependent manner. In addition, the 16s rDNA Sequencing analysis showed that 150 mg/kg LBP feeding may significantly increase the richness of gut microbiota by up-regulation of the ACE and Chao1 index and altered β-diversity among groups.
Lycium chinense extract Polysaccharides
Anti-obesity andhypolipidemiceffects of Lycium chinense leaf powder in obese rats
This study aimed to elucidate the obesity control,hypolipidemic, and antioxidanteffects of Lycium chinense leaf powder intake by obese rats. Obesity was induced in rats through 13 weeks ofhigh-fatdiet. The obese rats were then divided into four different groups, which were fed for 8 weeks with generaldiet (G),high-fatdiet (F), 5% L. chinense leaf powder with ahigh-fatdiet (FLP5), or 10% L. chinense leaf powder with ahigh-fatdiet (FLP10). The body weight gain of the FLP5 group was significantly lower than that of the F group. Also, the obesity index of the FLP5 and FLP10 group was significantly lower than that of the F group.serum Triglyceride and low-density lipoprotein (LDL)-cholesterol levels in the FLP5 group were significantly lower than those of the F group. The intake of L. chinense leaf powder did not seem to significantly affect the levels ofserum homocysteine, leptin, and ghrelin compared to the control group without L. chinense leaf powder intake. The glutathione content in the liver was significantlyhigher in the FLP5 group than in the G group, but the glutathione S-transferase activity was significantly lower than in the F group. The thiobarbituric acid-reactive substances levels in the liver and kidney were relatively lower in the FLP5 and FLP10 groups than in the G group. In summary, intake of L. chinense leaf powder in obese rats coincided with alowering of body weight and levels ofserum Triglyceride andLDL-cholesterol. It also displayed antioxidanteffects.
Hypoglycemic effect of lycium was confirmed in alloxan-induced diabetic mice, and a decrease in blood cholesterol and Triglyceride level was also observed [24].
Chapter 3.21 – Goji Berry (Lycium barbarum)— A Superfood
Lycium barbarum enhances the efficacy of the cardiovascular system, joint and muscle function, gastrointestinal tract regularity, and neurological/psychological traits. L. barbarum fruit has been shown to stimulate metabolism. Also, experiments conducted on rats showed a significant increase in the maximum combined capacity of cardiac muscle β-receptors with the administration of L. barbarum. The abundance of zeaxanthin in L. barbarum is effective in preventing particular eye diseases and is also beneficial for the general well-being of the eye. The efficacy of L. barbarum fruit and L. barbarum polysaccharide (LBP) as an antioxidant was proved by several clinical studies to exhibit protective effects against various peroxidation related conditions. L. barbarum fruit and LBP have a widespread diversity of immunomodulatory roles comprising the initiation of various immune cells. In this chapter, we highlighted its sources, traditional uses, health effects, and its possible interactions with drugs, foods, and other supplements.
Lycopene
Naturally OccurringPCSK9Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Background
Cardiovascular disease is associated with oxidative stress, inflammatory processes, and vascular dysfunction. Lycopene, a carotenoid found in tomatoes, is an antioxidant with a protectiveeffect onlipid peroxidation andAnti-atherosclerotic capacity. This review summarises current evidence on theeffect of lycopene onserumlipid concentrations andblood pressure.
Methods
We searched the PubMed and Cochrane databases for intervention studies between 1955 and September 2010 investigating theeffect of lycopene onbloodlipids orblood pressure for a minimum duration of 2 weeks. We conducted meta-analyses using a randomeffect model of all studies fitting the inclusion criteria. Additionally, we conducted subgroup meta-analysis ofserumlipid concentrations by lycopene dosage and subgroup meta-analysis by baselineblood pressure.
Results
Twelve studies (13 trial arms) meeting the inclusion criteria investigated theeffect of lycopene onserumlipids, and four studies examined itseffect onblood pressure. Meta-analysis onserumlipids revealed a significantcholesterol-loweringeffect of lycopene for totalserumcholesterol (mean change ± SE: −7.55 ± 6.15 mg/dl; p = 0.02) and low-density-lipoprotein (LDL)cholesterol (mean change ± SE: −10.35 ± 5.64 mg/dl, p = 0.0003) in the subgroup of trials using lycopene dosages of ≥25 mg daily, whereas subgroup meta-analysis of trials using lower lycopene dosages was not significant. Meta-analysis of theeffect of lycopene on systolicblood pressure of all trials suggested a significantblood pressurereducingeffect (mean systolicblood pressure change ± SE: −5.60 ± 5.26 mm Hg, p = 0.04).
Conclusions
Our meta-analysis suggests that lycopene taken in doses ≥25 mg daily iseffective inreducingLDLcholesterol by about 10% which is comparable to theeffect of low doses of statins in patient with slightly elevatedcholesterol levels. More research is needed to confirm suggested beneficialeffects on totalserumcholesterol and systolicblood pressure.
This work assessed the effects of a 28-day treatment with lycopene-rich extract (LRE) from red guava fruit (Psidium guajava L.) on the lipid profile and oxidative stress in an experimental model of dyslipidemia. Male hamsters (116.5 ± 2.16 g) were fed with the AIN 93G diet containing casein (20%), coconut fat (13.5%) and cholesterol (0.1%). The animals were divided into four groups: normolipidemic control (standard feed; NC, n = 7); hypercholesterolemic control (HC, n = 7); LRE 25 mg/kg/day (LRE-25, n = 7) and LRE 50 mg/kg/day (LRE-50, n = 9). After treatment, plasma concentrations of Triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol (LDL-c), high-density lipoprotein (HDL) cholesterol (HDL-c), malondialdehyde (MDA-p) and myeloperoxidase (MPO), as well as erythrocytic superoxide dismutase (SOD-e) and the atherogenic index, were determined. Malondialdehyde (MDA-h), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD-h) levels were assessed. Feed intake (FI) and weight gain (WG) were also determined. The LRE-25 group presented significantly lower TG levels and atherogenic index than did the HC group (p < 0.05). Both LRE-25 and LRE-50 groups presented lower levels of MDA-p and MPO than did the HC group (p < 0.05). LRE demonstrated a promising effect against dyslipidemia and oxidative stress.
Madhuca longifolia bark extract
Background: Madhuca longifolia (mahua) is a tropically growing tree found in various parts of India mostly on plain lands. The tree is considered a boon by the tribals who are forest dwellers because of its manifold medicinal properties. Studies show that in animals, alcoholic extracts of this tree produce beneficialeffects on diabetic andlipid profile. It is the purpose of this study to know whether these beneficialeffects are observed in Santhals many of whom are regular consumers of Madhuca longifolia drinks.
Methods: Diabetic andlipid profile ofblood along with standard anthropometric parameters were measured in a population of Santhal tribe (only males were chosen) many of whom, but not all, are regular consumers of mahua drinks. These findings were statistically analysed and compared using student’s t-test and inference drawn.
Results: Results show that anthropometric parameters do not differ much, but FBS. HbA1c,cholesterol andLDL these parameters are lower in mahua consumers compared to those in non-consumers. HDL is raised in mahua consumers compared to the other group. No significanteffect was observed in case of VLDL and Triglycerides .
Conclusions: Study shows that regular mahua drinks among Santhal tribe do improve diabetic andlipid profile, except Triglycerides and VLDL. Further and more elaborate studies are needed to have proper insight and practical gains in this regard.
Mangifera indica
Introduction:
cholesterollowering activity of Mangifera indica L. has been determined by earlier researchers and kernel, leaf and bark have shown significant activity. However, the specificcholesterollowering activity of leaf methanol extract has not been determined.
Materials and Methods:
The present study involved evaluation ofcholesterollowering potential of methanol extract of M. indica leaves usinghighcholesteroldiet model in albino Wistar rats. The acute oral toxicity at a dose of 5000 mg/ kg body weight was also determined in female albino Wistar rats. Phytoconstituents Iriflophenone 3-C-β-D-glucoside and mangiferin were quantified in methanol extracts of different varieties of mango leaves usinghigh performance liquid chromatography.
Results and Discussion:
Significantcholesterollowering activity was observed with methanol extract of M. indica leaves, at dose of 90 mg/kg body weight in rats and it was also found to be safe at dose of 5000 mg/kg rat body. Iriflophenone 3-C-β-D-glucoside and mangiferin were found to be in the range of 1.2 to 2.8% w/w and 3.9 to 4.6% w/w, respectively which along with 3 β taraxerol and other sterols could be contributing to thecholesterollowering activity of mango leaves extract.
Conclusions:
The phytosterols rich extract of Mangifera indica leaves is a good source of nutraceutical ingredient that have the potential to lowerserumcholesterol levels.
The methanol extract of M. indica showed a significant cholesterol-lowering activity at 90 mg/kg from day 21 to day 42 of 6 weeks treatment period, and a significant decrease in plasma Triglycerides was also observed on treatment with extract. The 3β-taraxerol, mangiferin, and iriflophenone-3-C-β-glucoside quantified in leaf methanol extract by HPLC and were found to be 0.49% w/w, 4.6% w/w, and 2.37% w/w, respectively. The methanol extract of M. indica leaf was found to be safe after oral administration of single dose of 5000 mg/kg body weight to female albino Wistar rats.
Mangifera indica L. Leaf Extract Induces Adiponectin and Regulates Adipogenesis
Our data showed that MLE possessed a high concentration of total polyphenols and phytochemical compounds; in particular, among all of them, we found a high content of mangiferin, myo-inositol and γ-oryzanol (Orz). Myo-inositol is a stereoisomer of inositol, a polyol belongs to vitamin B, that is currently used for the treatment of polycystic ovary syndrome [28]. Previous studies showed that myo-inositol regulates glucose metabolism and transport [29], moreover, Shorkpour et al., showed that Myo-inositol supplementation in women with polycystic ovary syndrome, compared with metformin, significantly reduced fasting plasma glucose, serum insulin levels, homeostasis model of assessment-insulin resistance, serum Triglycerides, and significantly increased the quantitative insulin sensitivity check index compared with metformin.
Mango ginger (Curcuma amada Roxb.)
Mango ginger (Curcuma amada Roxb.) is a spice commonly consumed in Asian countries. Health beneficial hypoTriglyceride mic property of mango ginger has been reported earlier. In this investigation, the anti-hypercholesterolemic influence ofdietary mango ginger was evaluated in experimental rats.dietary mango ginger powder (10%) or its equivalent of 10 mg% curcumin-containing portion was fed along with 1%cholesterol supplementeddiet in Wistar rats for 5 weeks. The treatment countered the liver andserum total andLDL + VLDL associatedcholesterols and increased the HDL associatedcholesterol while it had no influence oncholesterol levels in animals, maintained on normaldiet.dietary C. amada and its curcumin-free portion wereeffective inlowering livercholesterol in animals, maintained on basaldiet, while the curcumin-containing component of C. amada was ineffective. The biliary secretion of totallipids and bile acids was increased bydietary C. amada and both of its components. While biliarycholesterol was increased in animals fed with whole mango ginger, no such increases were noticed in groups fed with either components of mango ginger.cholesterolabsorption in ligated rat intestinal loops was not affected by mango ginger or either of its components. Thus, the present study has evidenced that the spice mango ginger possesses beneficial anti- hypercholesterolemic activity in hypercholesterolemic situation. This information is complementary to the earlier report on the health beneficial hypoTriglyceride mic influence of this spice.
When 10 percent dry mango ginger was fed in normal diets to adult female Wistar rats for 4 weeks, the liver, serum total and [VLDL+LDL] Triglycerides were lowered. In animals which were rendered hyperTriglyceridemic by feeding a sucrose-rich diet and subsequently fed the mango ginger diet, the liver or serum Triglyceride only tended to be lower. In mango ginger fed animals, the increase in liver and blood lipids after Triton WR-1339 treatment were significantly lower than in control diet fed animals. This effect of mango ginger was also observed in animals fed the equivalent of 0.3% curcumin-free extract but not in those fed the 10% curcumin containing portion of mango ginger. In both these groups, the lipoprotein lipase activities were elevated as with mango ginger fed group. The hypoTriglyceridemic activity of mango ginger appears to be mediated through influences on both liver synthesis and blood clearance.
When 10 percent dry mango ginger was fed in normal diets to adult female Wistar rats for 4 weeks, the liver, serum total and [VLDL+LDL] Triglycerides were lowered. In animals which were rendered hyperTriglyceridemic by feeding a sucrose-rich diet and subsequently fed the mango ginger diet, the liver or serum Triglyceride only tended to be lower. In mango ginger fed animals, the increase in liver and blood lipids after Triton WR-1339 treatment were significantly lower than in control diet fed animals. This effect of mango ginger was also observed in animals fed the equivalent of 0.3% curcumin-free extract but not in those fed the 10% curcumin containing portion of mango ginger. In both these groups, the lipoprotein lipase activities were elevated as with mango ginger fed group. The hypoTriglyceridemic activity of mango ginger appears to be mediated through influences on both liver synthesis and blood clearance.
Curcuma amada Roxb. is an important species known as mango ginger due to its characteristic raw-mango aroma. It has a long history of traditional uses ranging from folk medicine to several culinary preparations. The phytochemical, pharmacological and ethnobotanical studies of C. amada are reviewed. The rhizome is rich in essential oils, and more than 130 chemical constituents with biomedical significance have been isolated from it. Its antibacterial, insecticidal, antifungal and antioxidant properties have been investigated. The conservation of indigenous knowledge by proper documentation is suggested. The chemotaxonomy, allelopathy and genetic diversity of C. amada have not yet been explored, and many such studies are possible. This review was compiled to provide consolidated information covering different aspects of the plant, to provide a basis on which to plan future studies and to promote sustainable use of C. amada.
Medicago sativa L.extract
Increasedserumcholesterol andLDLcholesterol were reduced by 38 – 41.7% and 48 – 53.3% respectively when fed with alfalfa seed extract from the beginning or in established hyperlipidaemic model.LDL-cholesterollowering was maximum (64.4%) in a model fed with alfalfa meals withoutcholesterol. An increase in HDL-cholesterol totalcholesterol is suggestive of beneficial role since it is associated with low incidence ofAtherosclerosis. Possible mechanism oflipidlowering activity of Medicago sativa seed extract is worked out.
Alfalfa was reported to behypocholesterolemic andAntiatherosclerotic. Saponin glycosides were suggested to be responsible for this activity by neutralizingcholesterol in the stomach, enabling it to be excreted from the body. This makes alfalfa superior to the current anti-cholesterol medications which act by blockingcholesterol synthesizing apparatus. This study was undertaken in an attempt to prepare an alfalfa extract withhigh saponin content and free or low content of other toxic constituents found in alfalfa (canavanine and coumestrol), which causes serious sideeffects. A patent process was used to render alfalfa toxin free and to produce a drug present in the international market. Our study is based on monitoring the Egyptian crop at two different localities for its saponin, canavanine and coumestrol contents at different growth stages. The study showed that the tested extract of the chosen stage to be biologically studied (hypocholesterolemic andAntiatheroscleroticeffects) on the basis of thehighest saponin content was just before fruiting stage of the locality A. This stage was free from both coumestrol and canavanine. The study proved that the Egyptian crop of alfalfa was found to safely reduce naturalcholesterol and to possess a strongAntiatherosclerotic activity. This extract (I) produced the most significant decrease in totalcholesterol andLDL-cholesterol by 85.1 and 88%, respectively, of the corresponding levels in hypercholesterolemic rabbits. This decrease is more significant than that produced by gemfibrozil (73 and 74%) upon concomitant administration with a cho-lesterol enricheddiet using the same animal model at the tested dose level. Also, it was obvious that all alfalfa preparations produced
significant antioxidant properties. All alfalfa extracts possessedAntiatherosclerotic activity as observed by the almost normalization of the aortic sections upon concomitant use of alfalfa extracts withcholesterol-enricheddiet.
Melinjo (Gnetum gnemon) seeds
Objectives: Melinjo (Gnetum gnemon) seeds have been known to have some biological properties. One of them is ant hypercholesterolemia. The present study investigated in vitro and in silico methods to predict potential anti hypercholesterolemic of the Melinjo seed extracts of through HMG-CoA reductaseInhibitory activity. Methods: Melinjo seed powders were successively extracted by reflux method using five solvents with gradient polarity including: n-hexane, dichloromethane, ethyl acetate and methanol. All extracts were evaluated in vitro using HMG-CoA Reductase assay kit, to analyze theInhibitory activity. Molecular docking of the phytochemical content of the seeds were carried out using Auto Dock Vina, and also Ligand Scout to analyses interaction between ligand and receptor. Results: Dichloromethane extract demonstrated thehighestInhibitory activity against HMG-CoA reductase with IC50 value is 0.40 μg/mL, followed by that of ethyl acetate extract. UPLC-MS analyses showed that dichloromethane extract contained trans-resveratrol, piceid, gnetin C, gnetol, isorhapontigenin, ɛ-viniferin, gnemonol L, and gnemonol M. Molecular docking studies demonstrated that dimer of resveratrol such as gnemonol L, gnemosida, and ɛ-viniferin have better free binding energy than that of monomer. piceid, gnetin C, gnemonol L, and gnemonol M could be considered as HMG-CoA reductaseInhibitor. Conclusion: Gnetum gnemon seed extract showed strong HMG-CoA reductase activity. Resveratrol dimer promises as a potential lead compound to design/synthesize anti-cholesterol.
Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been proposed as an anti-obesity strategy. However, it remains unclear how MSE modulates energy balance. We tested the hypothesis that dietary MSE reduces energy intake and/or increases physical activity and metabolic thermogenesis in brown and white adipose tissue (BAT and WAT) in mice. Twenty-four C57BL/6 J mice were provided with normal diet, high-fat diet (HFD), or HFD with 1% MSE added, for 17 weeks. Food intake, spontaneous locomotor activity, hepatic Triglyceride (TG) content, and blood parameters were examined. Mitochondrial thermogenesis-associated molecule and inflammatory marker expression levels in BAT and WAT were examined by quantitative PCR and western blotting. Dietary MSE did not affect energy intake or spontaneous locomotor activity, but significantly suppressed HFD-induced fat accumulation, hyperglycemia, and hyperinsulinemia. Homeostasis model assessment of insulin resistance score and hepatic TG content were both lower in the MSE-supplemented HFD-fed group than in the HFD-fed group, indicating reduced insulin resistance and a less fatty liver. Dietary MSE upregulated thermogenic uncoupling protein 1 (UCP1) and mitochondrial marker cytochrome c oxidase subunit IV protein expression in BAT; this was closely associated with sirtuin 1 mRNA induction. mRNAs of adipose inflammatory markers, such as monocyte chemotactic 1 and interleukin-1, were induced by HFD but suppressed by MSE. Considering that UCP1 protein expression is the most physiologically relevant parameter to assess the thermogenic capacities of BAT, our results indicate that dietary MSE supplementation induces BAT thermogenesis and reduces obesity-associated adipose tissue inflammation, hepatic steatosis, and insulin resistance.
Melissa officinalis
Background
The purpose of this study was to investigate the safety andeffects of Melissa officinalis, a good source of bioactive components, onapolipoprotein (Apo)B, Apo A-I, and their ratio,lipids ratios and intercellular adhesion molecule-1(ICAM-1) in patients with type 2 diabetes.
Methods
For the present randomized, double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients aged 20–65 years old were randomly assigned to receive hydroalcoholic extract of M. officinalis (HEMO) (700 mg/d) or placebo twice-daily for 12 weeks.
Results
There were significant differences inserum Apo A-I, TC/ HDL-c andLDL-c/ HDL-c between the two groups at the end of the study (p < 0.05), but we did not show significant differences in the values for Apo B, Apo B/Apo A-I, TG/HDL-c, ICAM-1 and liver enzymes include AST, ALT, and ALP between the study groups. Although both groups showed a significant reduction in ICAM-1, AST and, ALP (p < 0.05), no significant differences in ICAM-1, AST and, ALP were observed. At end, in M. officinalis group, there was a significant increase in Apo A-I (p = 0.003) and significant reduction in TG/HDL-c (p = 0.05) compared with initial values, as well as in placebo group, there was a significant rising in Apo B/Apo A-I (p = 0.02) and significant reduction in Apo A-I (p = 0.001) compared with baseline values.
Conclusions
M. officinalis is safe andeffective in improvement of Apo A-I, Apo B/Apo A-I, andlipids ratios as key factors promoting cardiovascular disease (CVD) in type II diabetic patients.
Safe and significant effects in terms of decreasing the serum level of Triglyceride (TG) in all patients after 2 months (p-value=0.02) and in patients with higher baseline serum levels of TG (TG≥200 mg/dl) after 3 months (p-value=0.04) were shown in the MO group. However, no metabolic significant changes were seen compared to the control group. Significant decrease in both systolic and diastolic blood pressure from baseline values were also found in patients with higher systolic blood pressure (SBP≥130 mmHg) (p-value=0.02) and those with higher diastolic blood pressure (DBP≥85 mmHg) (p-value=0.02) in the MO group.
Miracle fruit (Synsepalum dulcificum)
Thecholesterol-lowering activity of miracle fruit (Synsepalum dulcificum)
Miracle fruit (Synsepalum dulcificum) is famous for its uniqueness of modifying sour taste to sweetness. However, itscholesterol-lowering activity has not been reported. This study investigated theeffect of S. dulcificum on the compositional changes of plasmalipids in hamsters fed ahigh-cholesterol controldiet. Six groups of hamsters were fed either a controldiet or one of the five experimentaldiets containing 2% ethanol extract of leaves, 2% water extract of leaves, 2% ethanolic extract of seeds (ES), 2% water extract of seeds, or 2% dry pulp. Results showed that ES decreased the plasma totalcholesterol (TC). Two triterpenoids (lupeol acetate and β-amyrin acetate) were isolated from the ES and they added to adiet could decrease TC by 15%–20% in hamsters. It was concluded that ES showed potent TC-lowering activity and triterpenoid was one of the active components of ES.
Practical applications
In recent years, people are more interested in phytochemicals from functional foods treated for hyperlipidemia because they possessed fewer sideeffects than the synthetic drugs. The triterpenoids isolated from the miracle fruit may be promising candidates for the development ofcholesterol-lowering agent, especially for patients whosebloodcholesterol level and body weight arehigh. Meanwhile, the miracle fruit have a good potential ascholesterol-lowering functional food or a natural source ofcholesterol-lowering agent.
Monacolin k
Hypercholesterolemia and elevated homocysteine concentrations are associated with cardiovascular risk. Previous studies have demonstrated acholesterol-loweringeffect of red yeast rice (RYR) supplements which contained 5 to 10 mg of monacolin K. We hypothesized that the intake of a low monacolin K dose may likewise reduce low-density lipoprotein-cholesterol (LDL-C) and other plasmalipids. In secondary analyses, we tested the homocysteineloweringeffect of folic acid, which was also included in the study preparation. Therefore, we conducted a randomized, double-blind, and placebo-controlled intervention study. One hundred forty-two nonstatin-treated participants with hypercholesterolemia (LDL-C ≥ 4.14 ≤ 5.69 mmol/L) were randomized to the supplement group with RYR or the placebo group. Participants of the supplement group consumed 3 mg monacolin K and 200 μg folic acid per day. A significant (P < .001) reduction ofLDL-C (-14.8%), totalcholesterol (-11.2%), and homocysteine (-12.5%) was determined in the supplement group after 12 weeks. A total of 51% of the participants treated with RYR achieved the limit ofLDL-C <4.14 mmol/L advised and 26% reached the threshold level of homocysteine <10 μmol/L. No significant changes were exhibited within the placebo group. Other parameters remained unchanged and no intolerances or serious adverse events were observed. In conclusion, we demonstrated that a low dose of daily 3 mg monacolin K from RYR reduces the concentration ofLDL-C; a risk factor for cardiovascular diseases.
The yeast Monascus purpureus, as a result of fermentation on rice, produces metabolically active components known as monacolin, the most representative one is the monacolin k, equipped withhigh affinity towards the enzyme HMG-CoA reductase. Meanwhile in literature it is widely reported as treatment with policosanol allows a reduction inblood ofcholesterol (LDL/tot), Triglycerides and, on the other hand, an increased level of HDL. Given these circumstances and considering the fact that the action of fermented rice by Monascus purpureus is given by a set of factors not strictly related to monacolin k itself, the objective of the MONAPOL clinical trial is to verify the profiles ofeffectiveness and tolerability of a galenic comparable to adietary supplement containing a dry extract of fermented red rice by Monascus purpureus associated with another one titrated in policosanol. The study is aimed, in a period of 3 months, for a representative cohort of 210 subjects presenting mild to moderate hypercholesterolemia uncomplicated unfamiliar (PCs currently outside indication comparing to the start of treatment withInhibitors of HMG-CoA reductase). At the Faculty of Pharmacy of University of Turin, the study of the formulation, the verification of stability of molecules present in the galenic and the preparation thereof, were conducted. Galenics present advantages such as the ability to use specific ingredients in order, firstly not to incur indietary intolerances, secondly the possibility to select the source of supply that best ensures thehigh quality of raw materials. The analytical HPLC method necessary for the pharmacokinetic study, already on going for enrolled patients, was set up. The benefit derived from treatment is considered as both absolute and percentage reduction compared to levels resulting in hematic withdrawal before the start of the study, oflipid metabolic disorder pathologies indexes;blood analysis of subjects were performed both by venipuncture and self-diagnostics device. Considering the new regulations on “Services Pharmacy” it seems appropriate and relevant to assess the reliability of self-diagnostics tools comparing the results obtained with those ones resulting from analyses carried out in authorized laboratories.
Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells
Monacolin K is the secondary metabolite iso- lated from Monascus spp. It is the natural form of lovastatin, which is clinically used to reduce the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase. In the present study, monacolin K increased pro-tein expression of SIRT1 and phosphorylation level of AMP-
activated protein kinase (AMPK) in HepG2 cells. Through activation of SIRT1/AMPK pathway, monacolin K increased phosphorylation of acetyl CoA carboxylase and caused nuclear translocation of forkhead box O1. The wes-tern blotting results showed that monacolin K increased expression of adipose Triglyceride lipase but decreased abundances of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1). Monacolin K also decreased the intracellular accumulation of lipids as demonstrated by Oil Red O staining. In addition, the immunostaining showed that monacolin K prevented the nuclear translocation of SREBP1, indicating the association with down-regulation of FAS. All the demonstrated effects of monacolin K were counteracted by nicotinamide or compound C, the inhibitors of SIRT1 or AMPK. In summary, monacolin K reduces the lipid content through SIRT1/ AMPK pathway in HepG2 cells, which promotes catabolism and inhibits anabolism of lipid.
Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, Triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.
Mori Folium leaves extract
Context: Folium Mori, the leaf of Morus alba L. (Moraceae), has been used in traditional Chinese medicine (TCM) for treating diabetes. However, it is unclear which components in the mulberry leaf areeffective for the treatment of type 2 diabetes mellitus (T2DM).
Objective: To investigate the flavonoids and polyphenols in mulberry leaves and their antihyperglycemic and antihyperlipidemiceffects in T2DM rats.
Materials and methods: Male Sprague-Dawley rats were divided into five groups: normal control (NC), diabetic control (DBC), diabetic group with 0.3 mg/kg b.w./day rosiglitazone (RSG), diabetic group with 7 g/kg b.w./day TCM formula and diabetic group with 2 g/kg b.w./day Folium Mori extract (FME). After 4 weeks, the rats were sacrificed; biochemical parameters, gene and protein expression were measured.
Results: The FBG level was significantly lower in the FME group than in the DBC group (p < 0.05). In oralglucose tolerance test, the AUC was significantly lower in the FME group (p < 0.05). The HOMA-IR level was significantly decreased in the FME group (p < 0.05). FME decreased the totalcholesterol (TC), Triglyceride (TG) and low density lipoprotein (LDL) levels (p < 0.05). FME increased the mRNA and protein expression of IRS-1, PI3K p85α and Glut-4 increased significantly (p < 0.05). Histological analysis revealed amelioration oflipid accumulation following FME treatment. Additionally, immunohistochemical analysis displayed stronger staining of Glut-4 in the FME group compared to the DBC group.
Discussion and conclusion: FME could decrease the body weight,bloodglucose, TG, TC andLDL levels, and improve insulin resistance. FME possessed significant antihyperglycemic and antihyperlipidemic activities via the IRS-1/PI3K/Glut-4 signalling pathway.
This study aimed to explore the effects of mulberry leaf powder on glucose metabolism as well as the underlying mechanisms. The largemouth bass (initial body weight: 10.12 ± 0.06 g) were randomly allotted into three treatments, fed low-starch diet (LS, 5%), high-starch diet (HS, 15 %) and high-starch diet with mulberry leaf powder (SM, 50 g/kg diet) for 8 weeks, respectively. Biochemistry parameters were tested using commercial biochemical kits, immune and antioxidant related genes expression were assessed using Q-PCR.The SM group exhibited significantly higher specific growth rate (SGR) and protein efficiency ratio (PER), and lower hepatosomatic index (HSI), liver lipid and glycogen contents than HS treatment. Simultaneously, the suppressed growth accompanied by impaired liver function was found in fish fed the HS diet compared to the LS group. However, supplementation with mulberry leaf diet (SM) significantly reduced plasma glucose, Triglyceride (TG) and total cholesterol (TC) contents, the activities of alanine aminotransferase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) compared with the HS group. Accordingly, the liver histological investigation showed an improvement of liver histostructure in the SM group. Furthermore, hepatic SOD and CAT were significantly up-regulated by SM supplementation. Meanwhile, the superoxide dismutase (SOD) and catalase (CAT) activities of SM group were significantly increased, while malondialdehyde (MDA) content significantly reduced in liver compared with the HS group. In addition, SM supplementation significantly down-regulated the expression levels of nf-kb, tnf-a and il-8 in the liver, while il-10 showed significant improvement in the LS group compared to the HS group. Mulberry leaves could alleviate hepatic injuries by regulating inflammation and oxidative stress, providing a theoretical basis for the development of mulberry leaves as a drug against high starch-induced liver disease.
Moringa oleifera Lam.leaves extract
effect of fruits of Moringa oleifera on thelipid profile of normal and hypercholesterolaemic rabbits
Rabbits were fed Moringa oleifera (200mg/kg/day, p.o.) or lovastatin (6mg/kg/day, p.o.) in banana pulp along with standard laboratorydiet and hypercholesterolaemicdiet for 120 days. Moringa oleifera and lovastatin were found to lower theserumcholesterol, phospholipid, Triglyceride , VLDL,LDL,cholesterol to phospholipid ratio and atherogenic index, but were found to increase the HDL ratio (HDL/HDL-totalcholesterol) as compared to the corresponding control groups. Treatment with M. oleifera or lovastatin in normal rabbits decreased the HDL levels. However, HDL levels were significantly increased or decreased in M. oleifera- or lovastatin-treated hypercholesterolaemic rabbits, respectively. Lovastatin- or M. oleifera-treated hypercholesterolaemic rabbits showed decrease inlipid profile of liver, heart and aorta while similar treatment of normal animals did not produce significant reduction in heart. Moringa oleifera was found to increase the excretion of faecalcholesterol. Thus, the study demonstrates that M. oleifera possesses a hypolipidaemiceffect.
Moringa oleifera is used in Thai traditional medicine as cardiotonic. Recent studies demonstrated its hypocholesterolaemiceffect. However, to be clinically useful, more scientific data are needed. Aim of the Study: We investigated the antioxidant, hypolipidaemic andAntiatherosclerotic activities of Moringa oleifera leaf extract. Materials and Methods: Scavenging activity of the extract on 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and theInhibitoryeffect on Cu2+-induced low-density lipoprotein (LDL) oxidation were determined in in vitro experiment. Theeffects of the extract oncholesterol levels, conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) and plaque formations incholesterol-fed rabbits were investigated.
Results: We found that in scavenging DPPH radicals the extract and Trolox® had IC50 of 78.15 ± 0.92 and 2.14 ± 0.12 μg/ml, respectively. The extract significantly (P < 0.05) prolonged the lag-time of CD formation and inhibited TBARS formation in both in vitro and ex vivo experiments in a dose-dependent manner. In hypercholesterol-fed rabbits, at 12 weeks of treatment, it significantly (P < 0.05) lowered thecholesterol levels and reduced the atherosclerotic plaque formation to about 50 and 86%, respectively. Theseeffects were at degrees comparable to those of simvastatin.
Conclusions: The results indicate that this plant possesses antioxidant, hypolipidaemic andAntiatherosclerotic activities and has therapeutic potential for the prevention of cardiovascular diseases.
ABSTRACT Objective: Moringa oleifera Lam. (Moringaceae), a small rapid growing, evergreen, deciduous tree is an important medicinal plant. Leaves and fruits of this plant are used for various ailments, as a nutritional supplement and also as vegetables. The current study involves in the determination of best combination of thecholesterol-lowering potential of a blend of methanol extracts of M. oleifera leaf and fruits, developed based on in vitro FIC index studies and evaluate the combination of this extracts in hypercholesterolemic animal models. Methods: Leaf and fruit methanol extracts and their combinations were tested in in vitro lipase inhibition assay to determine the best combination using fractionalInhibitory concentration (FIC) index. Hypercholesterolemia was induced with Triton WR-1339 (a non-ionic detergent) and withhighcholesteroldiet for acute and chronic model respectively and thecholesterol-loweringeffect of 1:1 blend of M. oleifera leaf and fruits methanol extracts was evaluated. Results: The FIC index values indicated that M. oleifera leaf and fruit extracts blended in 1:1 proportion was the best combination in in vitro lipase inhibition assay. This blend, when evaluated in vivo, showed a significant decrease inserum totalcholesterol level from 24 h through 48 h in triton model. Inhighcholesteroldiet model, the extract blend showed a significant reduction inserum Triglycerides levels at 3 and 6 w of treatment. Conclusion: The results indicate that the blend of M. oleifera at the tested dose could beloweringcholesterol and Triglyceride levels by inhibiting theabsorption ofcholesterol and can be developed as a standardized blend fordietary supplement market. Keywords: Moringa oleifera,cholesterol, Lipase, FIC, Triton,high-fatdiet, Niazirin
Antiretroviral drugs can have adverse effects. Most are manageable, but some can be serious. Moringa oleifera is a readily available plant with several use. The aim of this clinical study is to evaluate the potential benefits of taking Moringa oleifera on body mass index (BMI), blood Triglyceride and High density lipoprotein (HDL) level in patient taking Tenofovir/Lamivudine/efavirenz (TLE) combination. The study was designed as a Longitudinal Randomized Comparative Trial (LRCT) involving 140 HIV adult subjects (56 males, 84 females) who have been on Tenofovir/Lamivudine/efavirenz (300/300/600mg) TLE combination for at least 6 months prior to the study. They were recruited from a Teaching Hospital in Nigeria. Moringa oleifera capsules (200mg) were administered by the subjects to be used beginning from the first day of visit 0, through visit 1 (after four weeks) and 2 (after 12 weeks). Blood samples of subjects were collected at each visit (visit 0, 1 and 2) and analyzed for Triglyceride and HDL level. There was no significant reduction in serum HDL level (P<0.01) of subjects in visit 1 but there was significant (P<0.01) increase on visit 2 when compared to visit 0. There was also significant improvement in blood Triglyceride level (P<0.01) in visit 1 and 2 compared to visit 0 of tenofovir/Lamivudine/Efavirenz (TLE) moringa combination Results from the study suggests that Moringa oleifera may be useful in improving Triglyceride and cholesterol level of patients receiving TLE combination.
The main treatment for HIV is a class of drugs called antiretrovirals. Sticking to a treatment plan isn’t always easy. Antiretroviral drugs can cause side effects that can be severe enough to make some people stop taking them. A side effect can also get worse the longer a drug is taken. An example is change in metabolic parameters. The aim of this clinical study is to evaluate the potential benefits of taking Moringa oleifera on blood Triglyceride and cholesterol level in patient taking Tenofovir/Lamivudine/efavirenz (TLE) combination. The study was designed as a Longitudinal Randomized Comparative Trial (LRCT) involving 140 HIV adult subjects (56 males, 84 females) who have been on Tenofovir/Lamivudine/efavirenz (300/300/600mg) TLE combination for at least 6 months prior to the study. They were recruited from a Teaching Hospital in Nigeria. Moringa oleifera capsules (200mg) were administered by the subjects to be used beginning from the first day of visit 0, through visit 1 (after four weeks) and 2 (after 12 weeks). Blood samples of subjects were collected at each visit (visit 0, 1 and 2) and analyzed for Triglyceride and cholesterol level. There was significant reduction in blood Triglyceride and cholesterol level (P<0.01) of subjects in visit 1 and 2 when compared to visit 0. There was also significant improvement in blood Triglyceride and cholesterol level (P<0.01) in visit 2 compared to visit 0 of tenofovir/Lamivudine/Efavirenz (TLE) combination, when compared to subjects that did not received Moringa oleifera. There was no significant difference in the blood Triglyceride and cholesterol level (P<0.01) in the non moringa subjects. Results from the study suggests that Moringa oleifera may be useful in improving Triglyceride and cholesterol level of patients recieving TLE combination.
Morus alba
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, andcholesterol-lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellularcholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies forcholesterol-lowering in the food and medicine industries.
Anti-obesity and hypolipidemic effects of Morus alba
The pharmacological activity of UP601 (a mixture of Morus alba, Yerba mate and Magnolia officinalis extracts), was studied on changing of obesity-related parameters and biochemical markers in obesity induced in mice by high fructose (HFF). UP601at a dose of 250 mcg/ml, induced a 1.8-times increase in lipolysis. UP601decreasedbody weight by 9.1, 19.6 and 25.6%at doses of 300mg, 450mg and 600 mg/kgfor 7 weeks in rats. The same doses caused reduction in the total cholesterol 9.1, 16.9 and 18.6%; in Triglycerides 45.0, 55.0, 63.6%; in LDL 34.8, 37.1 and 41.6%;and in serum glucose 3.2, 21.6 and 33.7%, respectively. UP601 also caused 31.6% reduction in the body fat distribution and up to 89.1% decrease in the mesenteric fat.
Nutraceutical and Medicinal Potential of the Morus Species in Metabolic Dysfunctions
The effects of inflammation of leaves and fruit extracts of Morus alba were also observed in obese animals after 12 weeks of treatment, where there was a normalization of the NLRP3 inflammatory protein during the early stages of healing and accelerated healing when compared to animals that did not receive supplementation with the extracts. NLRP3 plays a key role in the induction of inflammation progression, since it triggers inflammatory cascades and decreases angiogenesis during the wound healing stages. Its control generates an improvement in the installed inflammation
Supplementation with Mulberry leaf feed (MF) significantly reduced serum Triglyceride and free cholesterol concentrations and increased the ratio of high-density lipoprotein cholesterol (HDL-c) to low-density lipoprotein cholesterol (LDL-c), while serum glucose and free fatty acids remained unchanged. Dietary MF resulted in a significant reduction in the size of adipocytes and backfat thickness (P < 0.05). Accordingly, hormone-sensitive lipase (HSL) in backfat was significantly up-regulated and fatty acid synthase (FAS) was down-regulated by MF supplementation (both P < 0.05). Furthermore, MF supplementation significantly elevated circulating leptin and adiponectin without influencing serum insulin and glucocorticoid. Moreover, significantly higher leptin receptor (Leptin-R) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were detected in MF-supplemented pigs, suggesting an enhanced leptin signaling induced by MF in the subcutaneous fat.
Protective effect of Morus rubra L. leaf extract on diet-induced atherosclerosis in diabetic rats
The antiatherosclerotic effect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath) diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mg cholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxic effects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fasting blood glucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight and serum lipid profile i.e., total cholesterol, Triglyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels and oxidized LDL), apolipoprotein A and apolipoprotein B were significantly (p<0.001) reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis of glucose and fat and possesses significant anti-atherosclerotic activity.
Morus laevigata
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, andcholesterol-lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellularcholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies forcholesterol-lowering in the food and medicine industries.
Morus multicaulis
The free and bound phenolic extracts of leaves from three mulberry species, Morus alba Linn., M. multicaulis Perr., and M. laevigata Wall. from Yunnan (China), were evaluated for the first time to examine their phenolic composition, antioxidant, andcholesterol-lowering capacity in HepG2 cells. The result showed that the total phenolic content of six extracts were ranged from 0.54 to 17.63 mg GAE/g DW, and the total flavonoids content varied from 0.52 to 35.62 mg RE/g DW. Chlorogenic acid, Rutin, and Catechin were the main compounds in the selected mulberries. The antioxidant properties in a positive correlation with the phenolic contents of mulberries were exhibited. The free phenolic extract of M. multicaulis Perr. significantly decrease the intracellularcholesterol content in HepG2 cells. In a word, the free phenolic extracts of M. multicaulis Perr. could be used as for further nutritional studies forcholesterol-lowering in the food and medicine industries.
Morus rubra
Protectiveeffect of Morus rubra L. leaf extract ondiet-inducedAtherosclerosis in diabetic rats
TheAntiatheroscleroticeffect of aqueous leaves extract of Morus rubra was studied in streptozotocin-induced diabetic rats fed with atherosclerotic (Ath)diet [1.5 ml olive oil containing 8 mg (3, 20,000 IU) vitamin D2 and 40 mgcholesterol] for 5 consecutive days. A short-term toxicity assessment was also conducted in healthy rats to examine toxiceffects of the extract. Oral administration of extract to diabetic rats (100, 200 and 400 mg/kg body weight per day for a period of 30 days) produced significant (p<0.001) fall in fastingbloodglucose (FBG) in a dose-dependent manner. Treatment with the extract (400 mg/kg) showed significant (p<0.001) improvement in body weight andserumlipid profile i.e., totalcholesterol, Triglyceride , HDL-cholesterol,LDL-cholesterol and VLDL-cholesterol, when compared with diabetic control. Endothelial dysfunction parameters (sVCAM-1, Fibrinogen, total NO levels andoxidizedLDL),apolipoprotein A andapolipoprotein B were significantly (p<0.001)reversed to near normal, following treatment with the extract. Thus, our study shows that aqueous leaf extract of Morus rubra (400 mg/kg) significantly improves the homeostasis ofglucose and fat and possesses significantAnti-atherosclerotic activity.
Musa sapientum L. extract
Diabetes mellitus affectslipid levels resulting in diabetic dyslipidemia as well as electrolyte loss from the body. Musa sapientum has been reported to possess antidiabetic properties. This study assessed thelipid profile and electrolyte composition in alloxan-induced diabetic rats treated with methanol leaf extract of M. sapientum (cMEMSL). Diabetes was induced with alloxan (120 mg/kg i.p.). Seventy-five male albino rats were divided into 5 groups of 15 rats each. Group 1 was control; groups 2-5 were made diabetic and treated with 0.2 ml 0.9% NaCl, cMEMSL (250 mg/kg and 500 mg/kg), and glibenclamide (5 mg/kg), respectively, for 14 days.blood samples were obtained from the retro orbital sinus after light anesthesia from 5 animals in each group on days 2, 7, and 14 forlipids and electrolyte analysis.lipid profile of diabetic treated (cMEMSL and glibenclamide) animals showed significant reduction (p < .05) in totalcholesterol, Triglyceride , and low density lipoprotein (LDL) levels. Thehigh density lipoprotein (HDL) level in the treatment groups increased significantly (p < .05) compared with diabetic untreated. Sodium, potassium, and phosphate ions significantly increased in all diabetic treatment groups while chloride ion significantly decreased compared with diabetic untreated. There was no significant difference in calcium and bicarbonate ion concentration in all the groups. This study has showed additional properties of Musa sapientum to include its ability to restore electrolyte balance, reducecholesterol, Triglyceride ,LDL, and increase the HDL levels in diabetic animals.
Hypolipidemic principle of the inflorescence stalk of plantain (Musa sapientum)
A pectin present in the juice of the inflorescence stalk of plantain (Musa sapientum) has been isolated. The material contained 32·4% hexoses and 52·5% uronic acid. On administration to rats fed both cholesterol free and cholesterol diet, this material showed significant lowering of cholesterol and Triglycerides in the serum, liver and aorta. There was decreased cholesterogenesis in the liver as was evident from decreased activity of hydroxymethylglutaryl coenzyme A reductase and decreased incorporation of labelled acetate into hepatic cholesterol. Hepatic bile acids showed significant increase and there was increased fecal excretion of neutral sterols and bile acids. Release of lipoproteins into the circulation was lower. The material also caused increase in the activity of lipoprotein lipase in the heart and adipose tissue and also of plasma lecithin: cholesterol acyl transferase.
Diabetes mellitus affects lipid levels resulting in diabetic dyslipidemia as well as electrolyte loss from the body. Musa sapientum has been reported to possess antidiabetic properties. This study assessed the lipid profile and electrolyte composition in alloxan-induced diabetic rats treated with methanol leaf extract of M. sapientum (cMEMSL). Diabetes was induced with alloxan (120 mg/kg i.p.). Seventy-five male albino rats were divided into 5 groups of 15 rats each. Group 1 was control; groups 2–5 were made diabetic and treated with 0.2 ml 0.9% NaCl, cMEMSL (250 mg/kg and 500 mg/kg), and glibenclamide (5 mg/kg), respectively, for 14 days. Blood samples were obtained from the retro orbital sinus after light anesthesia from 5 animals in each group on days 2, 7, and 14 for lipids and electrolyte analysis. Lipid profile of diabetic treated (cMEMSL and glibenclamide) animals showed significant reduction (p < .05) in total cholesterol, Triglyceride, and low density lipoprotein (LDL) levels. The high density lipoprotein (HDL) level in the treatment groups increased significantly (p < .05) compared with diabetic untreated. Sodium, potassium, and phosphate ions significantly increased in all diabetic treatment groups while chloride ion significantly decreased compared with diabetic untreated. There was no significant difference in calcium and bicarbonate ion concentration in all the groups. This study has showed additional properties of Musa sapientum to include its ability to restore electrolyte balance, reduce cholesterol, Triglyceride, LDL, and increase the HDL levels in diabetic animals.
Myrmecodia Platytyrae
Myrmecodia plant or ant-nest plant is from Rubiaceae family. Rubiaceae are mainly tropical woody plants, consist mostly of trees and shrubs and can be found in temperate regions. Myrmecodia platytyrea (MyP) are believed to have medicinal value. This study was designed in order to investigate theeffect of MyP extract as anti hypercholesterolemic agent. The results showed that treatment of MyP can significantly reduce (p<0.05) low density lipoprotein (LDL) compared to negative control group. The extract was significantly increase (p<0.05)high density lipoprotein (HDL) concentration compared to negative control group. Besides that, MyP increased fecalcholesterol and fecal bile compared to normal control group. It was also found thatlipid profile was significantly decreased (p<0.05) in MyP treatment group. All biochemistry data showed that MyP water extract was not toxic at all.
Type 2 diabetes mellitus (T2DM) is one of the main non-communicable chronic diseases that has many complications that compromise the quality of life. Hence, the need to find alternatives to replace the current therapy or as an adjuvant. Tubers of Myrmecodia platytytrea (Rubiaceae) has been used traditionally as an alternative therapy for the management of cancer and other inflammatory-related disorders. The aim of this study was to investigate the potency of M. platytytrea methanolic tuber extract (MPMTE) as an antihyperglycemic agent, in vivo. :The streptozotocin (STZ)-induced diabetic rats were treated orally with MPMTE (100, 200 and 400 mg/kg) and metformin (positive control, 100 mg/kg) daily for 14 days. Blood glucose level and other biochemistry analysis were conducted including histological examination on liver, kidney and pancreas. The STZ-induced diabetic rats treated with MPMTE (200 and 400 mg/kg) had significant decreased (p<0.05) in fasting blood glucose, total cholesterol, Triglycerides and low-density lipoprotein (LDL) with no significant changes in high-density lipoprotein (HDL) compared to STZ-induced untreated diabetic rats. Liver, kidney and pancreas were devoid of any damage caused by STZ. MPMTE had strong antihyperglycaemic activity and was protective against any STZ-induced organ damage. Thus, MPMTE can be further developed into an adjuvant therapy for diabetic patients.
Naringin
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Naringin enhancesreverse cholesterol transport inhigh fat/low streptozocin induced diabetic rats
Naringin, a citrus-derived flavonoid with antihyperglycemic, antihyperlipidemic, and antioxidant properties, is reported to be a useful nutraceutical in the management of diabetes and its complications. This study investigated the mechanism of antiatherogenic properties of naringin in type 2 diabetes (T2DM) usinghigh fat-low streptozocin rat model of T2DM. Rats were treated daily with 50, 100 and 200 mg/kg naringin orally for 21days. Levels of biomarkers of T2DM,lipid profile and activity of paraoxonase (PON) were assayed spectrophotometrically. The levels of expression of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr), scavenger receptor class B member 1 (Scarb1), aryl hydrocarbon receptor (Ahr), hepatic Lipase (Lipc), and lecithin-cholesterol acyltransferase (Lcat) were assessed using relativereverse transcriptase polymerase chain reaction technique. Naringin treatment resulted in a dose-dependent significant (p < 0.05) decrease in the levels of plasmacholesterol and Triglyceride from 84.84 ± 1.62 to 55.59 ± 1.50 mg/dL and 123.03 ± 15.11 to 55.00 ± 0.86 mg/dL, respectively, at 200 mg/kg naringin. In the liver, Scarb1 and Ahr were significantly (p < 0.05) upregulated at 200 mg/kg naringin while Lipc and Lcat were significantly (p < 0.05) upregulated by 50 mg/kg naringin. T2DM-induced decrease in PON activities in the plasma, liver and HDL was significantly (p < 0.05)reversed by 200 mg/kg naringin treatment. These genes play critical roles inreversecholesteroltransport and hence our results showed that the antiatherogenic property of naringin in T2DM involves enhancement ofreversecholesteroltransport and PON activity.
Negroamaro polyphenolic extract
Purpose
The aim of the study was to evaluate the vascular anti-inflammatoryeffects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action.
Methods
Human endothelial cells were incubated with increasing concentrations (1–50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1–25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial–monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1.
Results
Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress.
Conclusions
This study showed multiple anti-inflammatory andAnti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases includingAtherosclerosis.
Nattokinase
In addition to its anti-atherosclerotic effects, NK or natto extract also has a favorable effect on lipids. Using NK or natto extract containing NK, animal studies from various laboratories confirmed that NK has a hypolipidemic effect and significantly reduces elevated serum Triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels (LDL-C) (10–16). Our studies found that in patients with hyperlipidaemia, NK treatment (26 weeks at 6,000 FU) reduced TC, LDL-C and TG, and increased the level of high-density lipoprotein cholesterol (HDL-C)
Nelumbinis folium
hyperTriglyceride mia is a condition characterized byhigh Triglyceride levels and is a major risk factor for the development of cardiovascular diseases. The present study was designed to investigate theInhibitoryeffect of roasted Nelumbinis folium (RN), which is a medicinal substance produced by heating lotus leaves, onlipidmetabolism inhigh fat/cholesterol (HFC)diet-inducedhyperTriglyceride mia. Except for those in the control group, Sprague–Dawley rats were fed an HFCdiet for four weeks to inducehyperTriglyceride mia. During the next nine weeks, the control, regulardiet; HFC, HFCdiet, FLU, fluvastatin (3 mg/kg/day); RNL, RN (100 mg/kg/day); RNH, RN (200 mg/kg/day) were orally administered together with thediet, and the experiments were conducted for a total of 13 weeks. The weight of the epididymal adipose tissue, liver, and heart of rats in the HFCdiet group significantly increased compared to those in the control group butimproved in the RN-treated group. It was also confirmed that vascular function, which is damaged by an HFCdiet, wasimproved after RN treatment. The levels of insulin,glucose, Triglycerides , totalcholesterol, and low-density lipoprotein increased in the HFCdiet group compared to those in the control group, while the administration of RN attenuated these parameters. In addition, the administration of RN significantly reduced the gene expression of both LXR and SREBP-1, which indicated theInhibitoryeffect of the biosynthesis of Triglycerides caused by RN. The results indicated that RN administration resulted in an improvement in the overalllipidmetabolism and a decrease in the concentration of Triglycerides in the HFCdiet-induced rat model ofhyperTriglyceride mia. Therefore, our findings suggest that the RN can be a candidate material to provide a new direction for treatinghyperTriglyceride mia.
HyperTriglyceridemia is a condition characterized by high Triglyceride levels and is a major risk factor for the development of cardiovascular diseases. The present study was designed to investigate the inhibitory effect of roasted Nelumbinis folium (RN), which is a medicinal substance produced by heating lotus leaves, on lipid metabolism in high fat/cholesterol (HFC) diet-induced hyperTriglyceridemia. Except for those in the control group, Sprague-Dawley rats were fed an HFC diet for four weeks to induce hyperTriglyceridemia. During the next nine weeks, the control, regular diet; HFC, HFC diet, FLU, fluvastatin (3 mg/kg/day); RNL, RN (100 mg/kg/day); RNH, RN (200 mg/kg/day) were orally administered together with the diet, and the experiments were conducted for a total of 13 weeks. The weight of the epididymal adipose tissue, liver, and heart of rats in the HFC diet group significantly increased compared to those in the control group but improved in the RN-treated group. It was also confirmed that vascular function, which is damaged by an HFC diet, was improved after RN treatment. The levels of insulin, glucose, Triglycerides, total cholesterol, and low-density lipoprotein increased in the HFC diet group compared to those in the control group, while the administration of RN attenuated these parameters. In addition, the administration of RN significantly reduced the gene expression of both LXR and SREBP-1, which indicated the inhibitory effect of the biosynthesis of Triglycerides caused by RN. The results indicated that RN administration resulted in an improvement in the overall lipid metabolism and a decrease in the concentration of Triglycerides in the HFC diet-induced rat model of hyperTriglyceridemia. Therefore, our findings suggest that the RN can be a candidate material to provide a new direction for treating hyperTriglyceridemia.
Nelumbo nucifera Gaertn is widespread and a popular food in central and southern Taiwan. It has also been reported to possess different therapeutic effects, but the effects of N. nucifera leaf on lipid metabolism and liver function remain unclear. In this study, a high fat diet was used to induce hyperlipidemia, hypercholesterolemia, and fatty liver in hamster. The effects of flavonoid-enriched N. nucifera leaf extract supplement and two lipid-lowing drugs, silymarin and simvastatin, on the disorders induced by high fat diet were investigated. The results showed that a 10-week application of a high fat diet to hamsters led to significant increases of body weight, plasma lipid derivatives (Triglyceride, total cholesterol, and lipoproteins), lipid peroxidation, and liver damage markers (plasma aspartate aminotransferase and alanine aminotransferase). Interestingly, flavonoid-enriched N. nucifera leaf extract supplement effectively ameliorated the high fat diet-induced lipid metabolic disorders as significantly as silymarin and simvastatin did. Moreover, the flavonoid-enriched supplement alleviated the high fat diet-induced accumulation of lipids in liver, the findings showing distinguishing mechanisms from the effects of silymarin and simvastatin. These results suggested that the flavonoid-enriched N. nucifera leaf extract supplement may significantly improve the high fat diet-induced abnormal blood lipids and liver damage as significantly as the common drugs. Consequently, it is suggested that the flavonoid-enriched N. nucifera leaf extract supplement is beneficial for the improvement of lipid metabolisms and the alleviation of liver damage in high fat diet treatment.
Nelumbo nucifera
Browning of fresh-cut plants is mainly attributed to the enzymatic browning of phenolic compounds induced by polyphenol oxidase (PPO), producing browning products such as anthraquinones, flavanol oxides, and glycosides, which are usually considered to be non-toxic. Could browning bring any benefits on behalf of their bioactivity? Our previous study found that browned lotus root extracts (BLREs) could reduce thecholesterol level in obese mice as fresh lotus root extracts (FLREs) did. This study aimed to compare the mechanisms of FLRE and BLRE oncholesterolmetabolism and verify whether the main component’s monomer regulatescholesterolmetabolism like the extracts do through in vitro experiments. Extracts and monomeric compounds are applied to HepG2 cells induced by free fatty acids (FFA). Extracellular totalcholesterol (TC) and Triglyceride (TG) levels were also detected. In addition, RT-PCR and Western blot were used to observecholesterolmetabolism-related gene and protein expression. The in vitro results showed that BLRE and FLRE could reduce TC and Triglyceride levels in HepG2 cells. In addition, BLRE suppressed the synthesis ofcholesterol. Meanwhile, FLRE promoted the synthesis of bile acid (BA) as well as the clearance andefflux ofcholesterol. Furthermore, the main monomers of BLRE also decreasedcholesterol synthesis, which is the same as BLRE. In addition, the main monomers of FLRE promoted the synthesis of BAs, similar to FLRE. BLRE and FLRE promotecholesterolmetabolism by different pathways.
Ethnopharmacological relevance: Nelumbo nucifera Gaertn. leaves have been used as medicinal herbs in the past 1300 years, specifically utilized to cure hyperlipidemia, hyperglycemia, and obesity. It has been recorded in the most famous medicinal book in China for more than 400 years. The present study aims to identify the potential therapeutic activities of the flavonoids isolated from Nelumbo nucifera leaves.
Materials and methods: Nelumbo nucifera leaf flavonoids (NLF) were tested for the inhibition of lipase, α-glucosidase, and α-amylase activities in vitro. A single dose of NLF was administered by oral gavage in mice for acute toxicity. Wistar rats withhigh-fatdiet-induced hyperlipidemia and two other animal models were used to evaluate thehypolipidemiceffects of NLF.
Results: Our in vitro biochemistry tests revealed that the NLF showedhighInhibitory activity against porcine pancreatic lipase, α-amylase, and α-glucosidase with IC50 values of 0.38 ± 0.022, 2.20 ± 0.18, and 1.86 ± 0.018 mg/mL, respectively. Furthermore, the NLF significantly lowered thelipid components, such as the totalcholesterol, Triglycerides , low-density lipoproteincholesterol, and malondialdehyde, in various established in vivo systems and raised thehigh-density lipoproteincholesterol. Moreover, the NLF alleviatedhigh-fatdiet-inducedlipid accumulation in the liver.
Conclusions: The results demonstrate that NLFs caneffectivelyameliorate hyperlipidemia and inhibit the key enzymes related to type 2 diabetes mellitus. Our findings may provide new pharmacological basis for the treatment of hyperlipidemia, hyperglycemia, and obesity using NLFs.
EFFECT OF NELUMBO NUCIFERA FLOWERS ON PLASMA LIPIDS AND GLUCOSE IN YOUNG, MIDDLE-AGED AND AGED RATS
Summary In the present study, the effect of Nelumbo nucifera was assessed by determining changes in plasma lipids and glucose of young, middleaged and aged rats by virtue of its hypolipidemic properties. Male albino rats of Wistar strains were divided into six groups: groups 1, 3 and 5 were control young, middle-aged and aged rats received normal chow diet alone and groups 2, 4 and 6 were young, middleaged and aged rats administered with N. nucifera (1000 mg/kg body weight/bidose/day) mixed with normal chow diet for 4 weeks. The increased levels of total cholesterol, Triglycerides, free fatty acids, phospholipids, LDL cholesterol, VLDL cholesterol, glucose and a decreased in HDL cholesterol was observed in middle-aged and aged control rats when compared to young control rats. Administration of N. nucifera prevented the age associated changes on total cholesterol, Triglycerides, free fatty acids, phospholipids, LDL cholesterol, VLDL cholesterol and glucose. HDL cholesterol level was found to be increased significantly in young, middle-aged and aged rats after treatment with N. nucifera. These finding demonstrated that N. nucifera normalized the age associated altered levels of lipids and glucose status in middle-aged and aged rats thereby decreasing the risk factors for cardio vascular diseases during aging process.
Niacin
Objectives: This study sought to assess the efficacy of niacin forreducing cardiovascular disease (CVD) events, as indicated by the aggregate body of clinical trial evidence including data from the recently published AIM-high (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/high Triglycerides : Impact on Global Health Outcomes) trial.
Background: Previously available randomized clinical trial data assessing the clinical efficacy of niacin has been challenged by results from AIM-high, which failed to demonstrate a reduction in CVD event incidence in patients with established CVD treated with niacin as an adjunct to intensive simvastatin therapy.
Methods: Clinical trials of niacin, alone or combined with otherlipid-altering therapy, were identified via MEDLINE. Odds ratios (ORs) for CVD endpoints were calculated with a random-effects meta-analyses. Meta-regression modeled the relationship of differences in on-treatmenthigh-density lipoproteincholesterol with the magnitude ofeffect of niacin on CVD events.
Results: Eleven eligible trials including 9,959 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CVD event (OR: 0.66; 95% confidence interval [CI]: 0.49 to 0.89; p = 0.007) and major coronary heart disease event (OR: 0.75; 95% CI: 0.59 to 0.96; p = 0.02). No significant association was observed between niacin therapy and stroke incidence (OR: 0.88; 95% CI: 0.5 to 1.54; p = 0.65). The magnitude of on-treatmenthigh-density lipoproteincholesterol difference between treatment arms was not significantly associated with the magnitude of theeffect of niacin on outcomes.
Conclusions: The consensus perspective derived from available clinical data supports that niacin reduces CVD events and, further, that this may occur through a mechanism not reflected by changes inhigh-density lipoproteincholesterol concentration.
Niacin is considered to be a powerful drug for the treatment oflipid and lipoprotein abnormalities connected with “residual cardiovascular risk”, which persist inhigh-risk patients even when the target goals ofLDL-C are achieved with statin therapy. Recent large randomized clinical studies – AIM-high (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/high Triglycerides ) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) – delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients withhigh cardiovascular risk. Moreover, in these studies, several adverseeffects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying thehypolipidemic and antiatherogeniceffects of niacin as well as some limitations of the designs of the AIMhigh and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.
Niacin Therapy, HDLcholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?
high-density lipoproteincholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-high and HPS2-THRIVE, have shown that despite itseffects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverseeffects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP)Inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primaryapolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C andLDL particle measures.cholesterolefflux, the mechanism by which macrophages in vessel walls secretecholesterol outside cells, correlates with both surrogate end points and clinical events. Theeffects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDLcholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested.
Niacin: another look at an underutilized lipid-lowering medication
Niacin, or water-soluble vitamin B3, when given at pharmacologic doses, is a powerful lipid-altering agent. This drug, which lowers the levels of atherogenic, apolipoprotein-B-containing lipoproteins, is one of few medications that can raise the levels of atheroprotective HDL cholesterol. Niacin also has beneficial effects on other cardiovascular risk factors, including lipoprotein(a), C-reactive protein, platelet-activating factor acetylhydrolase, plasminogen activator inhibitor 1 and fibrinogen. Many clinical trials have confirmed the lipid effects of niacin treatment; however, its effects on cardiovascular outcomes have been called into question owing to the AIM-HIGH trial, which showed no benefit of niacin therapy on cardiovascular endpoints. Furthermore, use of niacin has historically been limited by tolerability issues. In addition to flushing, worsened hyperglycaemia among patients with diabetes mellitus has also been a concern with niacin therapy. This article reviews the utility of niacin including its mechanism of action, clinical trial data regarding cardiovascular outcomes, adverse effect profile and strategies to address these effects and improve compliance.
Nicotinic acid
Objective: To determine the efficacy of nicotinic acid on thelipid profile of diabetic and non diabetic rats.
Methods: This was an experimental study done at the Institute of Molecular Biology and Biotechnology, The University of Lahore, Pakistan between May 2010 to July 2010. Nicotinic acid was administered to a hypercholesterolemic group and a hypercholesterolemic + diabetic Group of Albino rats for 42 days and response to therapy was recorded on day 21 and day 42 of the experiment. Comparison among these two groups as well as three control groups was determined by Analysis of Variance (ANOVA) and differences were considered significant at (P<0.05). A total of 50 rats were included in the study.
Results:lipid profile of the hypercholesterolemic group as well as hypercholesterolemic + diabetic group as compared with the control groups showedhighly significant improvement on the day 21 and day 42 of the experiment. The values ofserum totalcholesterol (TC), Triglycerides (TG), low density lipoprotein (LDL)cholesterol and totallipids (TL) showedhighly significant decrease whereasserumhigh density lipoprotein (HDL)cholesterol showedhighly significant increase.
Conclusion: Nicotinic acid is the mosteffective agent available in increasing HDLcholesterol andloweringserum TC, Triglycerides (TG),LDLcholesterol and TL in hypercholesterolemic Diabetic and hypercholesterolemic non-diabetic Albino rats.
Influence of nicotinic acid on metabolism of cholesterol and Triglycerides in man
The mechanisms for the hypolipidemic action of nicotinic acid were examined in 12 patients with hyperlipidemia. Most patients were studied in the hospital on a metabolic ward. The first month was a control period followed by 1 month on nicotinic acid. During treatment with nicotinic acid, the Triglycerides (TG) decreased in total plasma by an average of 52% and in very low density lipoproteins (VLDL) by 36%. Transport rates of VLDL-TG were determined by multicompartmental analysis following injection of [3H]glycerol as a precursor. Nicotinic acid decreased transport (synthesis) of VLDL-TG by an average of 21%. Kinetic modeling of the VLDL-TG data suggested that the TG reduction was due to a decrease in TG content of VLDL and hence a reduction in lipoprotein size more than number. For the whole group, plasma cholesterol fell during nicotinic acid therapy by a mean of 22%. The drug produced no detectable changes in fecal excretions of cholesterol (neutral steroids) or bile acids. However, it induced a small but significant increment in hepatic secretion of biliary cholesterol that might have led to a net loss of cholesterol from the body even though this loss could not be detected by sterol balance. Despite this increase in outputs of biliary cholesterol, there was not a significant increase in molar % cholesterol or in % saturation of gallbladder bile. Therefore, it is doubtful that nicotinic acid enhances the risk for cholesterol gallstones.
Nuciferine
The purpose of this study was to investigate whetherdietary nuciferine affectslipidmetabolism in broiler chickens. Four treatment groups were made from 120 1-day-old broiler chickens including the basediet group (normal control [NC], supplemented with 0 mg/kg of nuciferine) and groups treated with 25 mg/kg, 100 mg/kg, and 400 mg/kg ofdietary nuciferine, which was supplemented for 42 d. The results showed that body weight, average daily weight gain, and absolute and relative fat and liver weight were significantly decreased with nuciferine supplementation. The plasma concentration of triiodothyronine, free triiodothyronine, thyroxine, and free thyroxine was significantly decreased in the nuciferine-supplemented group, but the plasma glucagon concentration was significantly increased. The plasma and hepatic Triglyceride (TG) and totalcholesterol (TC) concentrations were significantly decreased in the nuciferine group, but plasma and hepatic nonesterified fatty acid concentration, hepatic lipase activity, and hepatic glycogen content were significantly increased. Hepatic histological examination showed that fat cell volume and size in the 100 and 400 mg/kg group were smaller than those in the NC group. The fatty degeneration in the liver was decreased with nuciferine supplementation. The fat cell volume and size were shrunk in the nuciferine group.dietary nuciferine supplementation significantly decreased the gene expression level of HMGCR, SREBP2, ACC, and SPEBP-1C, but significantly increased the gene expression level of LXR-α, CYP7A1, and CPT-I. The results indicated that nuciferine exhibited strong reduced fat deposition activities and reflected not only by decrease of the concentration of Triglyceride and TC but also by reduction in the key gene expression level of HMGCR, SREBP2, ACC, and SPEBP-1c and elevation of the key gene expression level of LXR-α, CYP7A1, and CPT-I. Taken together, our results suggested that the ability of nuciferine onreducing fat deposition in broiler chickens by regulatinglipidmetabolism was associated with the balance of Triglyceride and TC concentration.
Nuciferine Prevents Hepatic Steatosis by Regulating lipidmetabolismin Diabetic Rat Model
Objective
This study investigatesthe nuciferine capacity to regulate the liver’slipidmetabolism regarding steatosis and injury in STZ-induced diabetic rats.
Materials and Methods
The rats were randomly divided into groups control, diabetic and nuciferine 200 mg/kg/ day treatment. After 4 days of STZ injection, the nuciferine group was treated and administered via oral gavages for 4 weeks. At the end of experiment,blood, liver, myocardial and muscular samples were collected.
Results
Nuciferine-treated significantly increased the body weight from 339.4g to 367.8g, but significantly decreased the food and water intake compared with diabetic rats. Also, the nuciferine-treated rats had significantly decreased TC, TG, and FFAs in the liver compared with the diabetic group, especially theserum markers ofbloodglucose. These were associated with the gene expression related to lipogenesis which was significantly down-regulated; the gene expression involved in lipolysis and fatty acid β-oxidation was significantly up-regulated. Discussion and
Conclusion
The data provide evidence that nuciferine supplementation could protect the liver by regulatinglipidmetabolism gene expression resulting in decreasing the steatosis and injury in diabetic rat. Thus, nuciferine could be developed as a diabetic adjuvant food additive in future.
Nuciferine prevents hepatic steatosis by regulating lipid metabolismin diabetic rat model
The plasma Triglyceride (TG), total cholesterol (TC) and glucose levels were measured using commercial kits (Tiangen, Nanjing, China) by enzymatic methods. The plasma free fatty acids (FFAs) concentration was measured using commercial kits and according to the specification strictly (Wako, Japan) by ACS-ACOD method. Plasma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were measured according to the commercial Elisa kit manufacturer’s protocol (Langdun Technologies Inc, Shanghai, China).
3T3-L1 preadipocytes were treated with 0∼20 μM nuciferine for 24∼120 h, the cell viability was assessed using CCK8. 3T3-L1 preadipocytes and human primary preadipocytes were then induced differentiation and the effects of nuciferine on the lipid metabolism in differentiating and fully differentiated adipocytes were observed by the methods of intracellular Triglyceride (TG) assay, Oil Red O staining, RT-qPCR and western blot. Transient transfection and dual luciferase reporter gene methods were used to assess the effects of nuciferine on FAS promoter activities.
Ocimum sanctum L.extract
Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms ofdiet given for four weeks, brought about significant changes in thelipid profile of normal albino rabbits. This resulted in significantlowering inserum totalcholesterol, Triglyceride , phospholipid andLDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents.
It has been reported that Ocimum sanctum L. (OS) leaves decreaseserumlipid profile in normal and diabetic animals. No experimental evidences support the anti-hyperlipidemic and antioxidative actions against hypercholesterolemia. Moreover the identity of the specific chemical ingredients in OS leaves responsible for these pharmacologicaleffects are unknown. Since OS leaves are rich in essential oil (EO). Therefore the present study was conducted to investigate the anti-hyperlipidemic and antioxidative activities of EO extracted from OS leaves in rats fed withhighcholesterol (HC)diet. EO was extracted by the hydrodistillation method and the chemical constituents were then identified by Gas Chromatography-Mass Spectrometry. The experiment was performed in Male Wistar rats fed with 2.5 g%(w/w) ofcholesteroldiet for seven weeks. During the last 3 weeks, rats were daily fed with EO. The results showed that phenyl propanoid compounds including eugenol and methyl eugenol were the major constituents of EO. EO suppressed thehighserumlipid profile and atherogenic index as well asserum lactate dehydrogenase and creatine kinase MB subunit without significanteffect onhighserum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in rats fed with HCdiet. In addition, EO was found to decrease thehigh levels of thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx) and superoxide dismutase (SOD) without impacting catalase (CAT) in the cardiac tissue while in the liver, it decreasedhigh level of TBARS without significantlyeffecting GPx, SOD and CAT. Histopathological results confirmed that EO preserved the myocardial tissue. It can be concluded that EO extracted from OS leaves haslipid-lowering and antioxidativeeffects that protect the heart against hypercholesterolemia. Eugenol that is contained in EO likely contribute to these pharmacologicaleffects.
Ocimum sanctum Linn. (also known as Tulsi) is a sacred Indian plant, the beneficial role of which, in obesity and diabetes is described traditionally. This is a randomized, parallel group, open label pilot study to investigate the effect of O. sanctum on metabolic and biochemical parameters in thirty overweight/obese subjects, divided into two groups A and B. Group A (n = 16) received one 250 mg capsule of Tulsi (O. sanctum) extract twice daily in empty stomach for 8 weeks and group B (n = 14) received no intervention. Statistically significant improvements in the values of serum Triglycerides (p = 0.019); low density lipoprotein (p = 0.001); high density lipoprotein (p = 0.001); very low density lipoprotein (p = 0.019); Body Mass Index, BMI (p = 0.005); plasma insulin (p = 0.021) and insulin resistance (p = 0.049) were observed after 8 weeks in the O. sanctum intervention group. The improvement in HDL-C in the intervention group when compared to the control group was also statistically significant (p = 0.037). There was no significant alteration of the liver enzymes SGOT and SGPT in both the intervention (p = 0.141; p = 0.074) and control arms (p = 0.102; p = 0.055) respectively. These observations clearly indicate the beneficial effects of O. sanctum on various biochemical parameters in young overweight/obese subjects.
It has been reported that Ocimum sanctum L. (OS) leaves decrease serum lipid profile in normal and diabetic animals. No experimental evidences support the anti-hyperlipidemic and antioxidative actions against hypercholesterolemia. Moreover the identity of the specific chemical ingredients in OS leaves responsible for these pharmacological effects are unknown. Since OS leaves are rich in essential oil (EO). Therefore the present study was conducted to investigate the anti-hyperlipidemic and antioxidative activities of EO extracted from OS leaves in rats fed with high cholesterol (HC) diet. EO was extracted by the hydrodistillation method and the chemical constituents were then identified by Gas Chromatography-Mass Spectrometry. The experiment was performed in Male Wistar rats fed with 2.5 g%(w/w) of cholesterol diet for seven weeks. During the last 3 weeks, rats were daily fed with EO. The results showed that phenyl propanoid compounds including eugenol and methyl eugenol were the major constituents of EO. EO suppressed the high serum lipid profile and atherogenic index as well as serum lactate dehydrogenase and creatine kinase MB subunit without significant effect on high serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in rats fed with HC diet. In addition, EO was found to decrease the high levels of thiobarbituric acid reactive substances (TBARS), glutathione peroxidase (GPx) and superoxide dismutase (SOD) without impacting catalase (CAT) in the cardiac tissue while in the liver, it decreased high level of TBARS without significantly effecting GPx, SOD and CAT. Histopathological results confirmed that EO preserved the myocardial tissue. It can be concluded that EO extracted from OS leaves has lipid-lowering and antioxidative effects that protect the heart against hypercholesterolemia. Eugenol that is contained in EO likely contribute to these pharmacological effects.
Oenothera villosa Thunb extract
Background
Studies have shown that evening primrose oil (EPO) supplementation might beeffective in improvinglipid profile, however, the results are inconsistent. This study was performed to determine the direction and magnitude of the EPOeffect on thelipid profile.
Methods
PubMed, Scopus, Cochrane Library, Embase and Web of Science databases and Google Scholar were searched up to September-2019. Meta-analysis was performed using the random-effects model.lipid profile includinghigh-density lipoprotein (HDL), totalcholesterol (TC), Triglyceride (TG), and low-density lipoprotein (LDL) was considered as the primary outcome.
Results
A total of 926 articles were identified through database searching, of which, six RCTs were included in the meta-analysis. There were six studies on HDL, TC, and Triglyceride and four studies onLDL. EPO supplementation had no significanteffect on TC, TG,LDL, and HDL. However, in subgroup analysis, a significant reduction in Triglyceride at a dose of ≤4 g/day (weighted mean difference [WMD] = −37.28 mg/dl; 95% CI: −73.53 to −1.03, p = .044) and a significant increase in HDL in hyperlipidemic subjects (WMD = 5.468 mg/dl; 95% CI: 1.323 to 9.614, p = .010) was found.
Conclusion
Oral intake of EPO at a dose of ≤4 g/day significantly reducesserum Triglyceride levels and significantly increases HDL levels in hyperlipidemic subjects.
Olea europaea seeds
Our previous work demonstrated the presence of compounds withhypocholesterolemic capacity in olive seeds. These compounds were extracted using CO2-expanded ethyl acetate and identified as tyrosol, hydroxytyrosol, and β-sitosterol using GC–MS. This work describes the extraction of these compounds from different olive seeds using pressurized ethyl acetate. Their solubility in ethyl acetate at temperatures ranging from 40–200 °C was theoretically predicted by Hansen solubility parameters. The content of these compounds was estimated by GC–MS, as well as, the reduction of the micellarcholesterol solubility (RMCS) capacity of extracts enabling to establish the optimum extraction temperature at 100 °C. A GC–MS method was developed and validated in terms of its analytical characteristics for a sensitive determination and quantification of tyrosol, hydroxytyrosol, and β-sitosterol in different olive seeds. Within varieties, Manzanilla seeds presented thehighest concentration of tyrosol, hydroxytyrosol, and the lowest concentration of β-sitosterol, as well as thehighest RMCS capacity.
Antidiabetic effect of Olea europaea L. in normal and diabetic rats
The antidiabetic effect of an alcohol extract of olive (Olea europaea L.) leaves was investigated in normal and streptozotocin-induced diabetic rats. The oral administration of the olive leaves extract (0.1, 0.25 and 0.5 g/kg body wt) for 14 days significantly decreased the serum glucose, total cholesterol, Triglycerides, urea, uric acid, creatinine, aspartate amino transferase (AST) and alanine amino transferase (ALT) while it increased the serum insulin in diabetic rats but not in normal rats (p < 0.05). A comparison was made between the action of olive leaves extract and glibenclamide (600 µg/kg), a known antidiabetic drug. The antidiabetic effect of the extract was more effective than that observed with glibenclamide.
Olive leaf extract
Background
The anti-atherogeniceffect of olive leaf extract is supposed to be related to its activities of anti-oxidation and anti-inflammation.
Aim of the study
To prove theeffect of anti-Atherosclerosis by olive leaf extract (OLE) and to elucidate the mechanism behind.
Methods
Twenty-four rabbits were assigned to the control,highlipiddiet (HLD) and OLE group that were fed with standarddiet, HLD and HLD supplemented with OLE, respectively.serum levels ofAtherosclerosis related markers, Triglyceride (TG), totalcholesterol (T-CHO), low density lipoproteincholesterol (LDL-C),high density lipoproteincholesterol (HDL-C) and malondialdehyde (MDA) were detected at the ends of week 2, 4 and 6. Surface lesions and thickness of intimas were measured at the end of week6. The protein and/or mRNA expressions of inflammation factors, monocyte chemoattractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, nuclear factor-kappa B (NF-κB) and tumor necrosis factor α (TNF-α) were investigated by immunohistochemistry and RT-PCR.
Results
Atherosclerotic lesions were found in the HLD and OLE groups but not in the control group. In comparison with that in the HLD group, reduced size and thickness of intima (0.31 ± 0.26 in the HLD group versus 0.10 ± 0.03 mm in the OLE group) were found in the OLE group. The MDA level, an indicator of antioxidant status, was 35.27 ± 15.37 in the HLD group and 20.63 ± 11.52 nmol/ml in the OLE group. The level of CHO, Triglyceride andLDL-C were 104.46 ± 30.34, 2.48 ± 1.11, 82.83 ± 28.44 mmol/l in the HLD group versus 83.03 ± 27.23, 1.84 ± 0.44, 59.51 ± 23.72 mmol/l in the OLE group. Down-regulated expressions of MCP-1, VCAM-1, NF-κB and TNF-α at both protein and mRNA level (P < 0.05) were also found with the administration of OLE.
Conclusion
This study proved theeffect of OLE on inhibition ofAtherosclerosis, which is related to the suppressed inflammatory response.
Chinese Olive (Canarium album L.) Fruit Extract Attenuates Metabolic Dysfunction in Diabetic Rats
Hyperglycemia and dysregulation of lipid metabolism play a crucial role in metabolic dysfunction. The aims of present study were to evaluate the ameliorative effect of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) on high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. CO-EtOAc, rich in gallic acid and ellagic acid, could markedly decreased the body weight and epididymal adipose mass. In addition, CO-EtOAc increased serum HDL-C levels, hepatic GSH levels, and antioxidant enzyme activities; lowered blood glucose, serum levels of total cholesterol (TC), Triglycerides (TG), bile acid, and tumor necrosis factor alpha (TNFα); and reduced TC and TG in liver. We further demonstrated that CO-EtOAc mildly suppressed hepatic levels of phosphorylated IRS-1, TNF-α, and IL-6, but enhanced Akt phosphorylation. The possible mechanisms of cholesterol metabolism were assessed by determining the expression of genes involved in cholesterol transportation, biosynthesis, and degradation. It was found that CO-EtOAc not only inhibited mRNA levels of SREBP-2, HMG-CoAR, SR-B1, and CYP7A1 but also increased the expression of genes, such as ABCA1 and LDLR that governed cholesterol efflux and cholesterol uptake. Moreover, the protein expressions of ABCA1 and LDLR were also significantly increased in the liver of rats supplemented with CO-EtOAc. We suggest that Chinese olive fruit may ameliorate metabolic dysfunction in diabetic rats under HFD challenge.
Pactimibe Sulfate
The objective of the present study was to determine whether a novel acyl-CoA:cholesterol acyltransferase (ACAT)Inhibitor, pactimibe sulfate (CS-505), could reduce atherosclerotic lesions beyond and independent of the reduction achieved bycholesterollowering alone from two different types of lesions. (1) Early lesion model. Twelve-week-oldapolipoprotein E (apoE)−/− mice were treated with 0.03 or 0.1% (w/w) CS-505, 0.1 or 0.3% avasimibe (CI-1011), or 3% cholestyramine for 12 weeks. Each treatment significantly reduced plasmacholesterol by a similar degree (43–48%). TheAntiatherosclerotic activity of 0.1% CS-505, however, was more efficacious than theeffects of the other treatments (90% versus 40–50%). (2) Advanced lesion model. Twenty-four-week-old apoE−/− mice were treated with 0.03 or 0.1% CS-505 or 0.1% CI-1011 for 12 weeks. CS-505 at 0.1% revealed enhanced lesion reduction compared with 0.1% CI-1011 (77% versus 54%), whereas the plasmacholesterol-loweringeffect of 0.1% CS-505 was almost the same as that of 0.1% CI-1011. Furthermore, immunohistochemical analysis demonstrated that CS-505 significantly reduced the number of macrophages and expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13. These data indicate that CS-505 can reduce and stabilize atherosclerotic lesions. ThisAntiatherosclerotic activity is exerted via bothcholesterollowering and direct ACAT inhibition in plaque macrophages.
Paeonia lactiflora Pall
Ethnopharmacological relevance: Total glucosides of paeony (TGP), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China. Inflammation plays a critical role in the development of atherosclerotic vascular disease. Risk of cardiovascular diseases is significantlyhigher in patients with RA than in normal population. It has a great significance to study theeffects of TGP onAtherosclerosis.
Aim of the study: To investigate theeffects of TGP onAtherosclerosis induced by excessive administration of vitamin D andcholesterol in rats and study the mechanisms involved.
Materials and methods:Atherosclerosis was induced by excessive administration of vitamin D andcholesterol in rats. TGP was intragastrically administered for 15 weeks. Theserum concentrations of totalcholesterol (TC), Triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) andhigh density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer.apolipoprotein A1 (ApoA1) andapolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy.
Results: Compared to controls, TGP significantly lowered theserum level of TC, TG,LDL-C, ApoB, TNF-alpha, IL-6 and CRP, increased the ratios of HDL-C/LDL-C and ApoA1/ApoB, decreased the intima-media thickness (IMT) of abdominal aortal wall andimproved the morphological change of the aorta.
Conclusions: TGP may attenuate the development of atherosclerotic disease. The beneficialeffects are associated with itsloweringbloodlipids and inhibiting the expression of inflammatory cytokines.
Atherosclerosis was induced by excessive administration of vitamin D and cholesterol in rats. TGP was intragastrically administered for 15 weeks. The serum concentrations of total cholesterol (TC), Triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) were measured by automatic biochemistry analyzer. Apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) were determined by immunoturbidimetry method, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay (ELISA) method. The morphological changes of aorta were observed with optical microscopy.
Paeonia Suffruticosa peel extract
With improvement in living standards and average life expectancy, atherosclerotic cardiovascular disease incidences and mortality have been increasing annually. Paeonia suffruticosa, a natural herb, has been used for the treatment of atherosclerotic cardiovascular disease for thousands of years in Eastern countries. Paeonol is an active ingredient extracted from Paeonia suffruticosa. Previous studies have extensively explored the clinical benefits of paeonol. However, comprehensive reviews on the cardiovascular protectiveeffects of paeonol have not been conducted. The current review summarizes studies reporting on the protectiveeffects of paeonol on the cardiovascular system. This study includes studies published in the last 10 years. The biological characteristics of Paeonia suffruticosa, pharmacological mechanisms of paeonol, and its toxicological and pharmacokinetic characteristics were explored. The findings of this study show that paeonol confers protection against atherosclerotic cardiovascular disease through various mechanisms, including inflammation, platelet aggregation,lipidmetabolism, mitochondria damage, endoplasmic reticulum stress, autophagy, and non-coding RNA. Further studies should be conducted to elucidate the cardiovascular benefits of paeonol.
Panax ginseng C.A.Mey.extract
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
The king of herbs, Panax ginseng, has been used widely as a therapeutic agent vis-à-vis its active pharmacological and physiological effects. Based on Chinese pharmacopeia Ben Cao Gang Mu and various pieces of literature, Panax ginseng was believed to exert active vascular protective effects through its antiobesity and anti-inflammation properties. We investigated the vascular protective effects of ginseng by administrating ginseng extracts to rats after the induction of diabetes. We found that Panax ginseng can restore diabetes-induced impaired vasorelaxation and can reduce serum Triglyceride but not cholesterol level in the diabetic rats. The ginseng extracts also suppressed the expression of atherosclerosis-related genes and altered the expression of lipid-related genes. The results provide evidence that Panax ginseng improves vascular dysfunction induced by diabetes and the protective effects may possibly be due to the downregulation of atherosclerosis-related genes and altered lipid metabolism, which help to restore normal endothelium functions.
Passiflora edulis Sims. seed extract
effects of Passiflora edulis on the metabolic profile of diabetic Wistar rat offspring
Dry extract of the genus Passiflora has been shown to help control glycemia andlipid levels. The objective of this study was to evaluate theeffects of passion fruit (P. edulis) on the biochemical profile of offspring from diabetic rats. Diabetes was induced by streptozotocin. The diabetes group consisted of 10 rats withglucose levels greater than 200 mg/dL; the nondiabetic (control) group consisted of 10 rats withglucose levels less than 120 mg/dL. After the diagnosis of diabetes, the mating phase was started. By day 21 of pregnancy, the offspring were born; the dams were kept in individual cages with their offspring until the weaning period. The offspring were then divided into 4 groups (n=15 each): G1 were offspring from control dams, G2 were offspring from treated nondiabetic dams, G3 were offspring from diabetic dams, and G4 were offspring from treated diabetic dams. For 30 consecutive days, G1 and G3 offspring were treated with vehicle (oral gavage) and G2 and G4 offspring were treated with passion fruit juice (oral gavage). After 30-day treatment, the animals were anesthetized and killed, andblood was drawn immediately for analysis of the biochemical profile (totalcholesterol,high-density lipoproteincholesterol, low-density lipoproteincholesterol, Triglycerides , andglucose). The G2 and G4 rats showed significantly reduced totalcholesterol, Triglyceride , and low-density lipoproteincholesterol levels and an increasedhigh-density lipoproteincholesterol level. The use of passion fruit juiceimprovedlipid profiles, suggesting that this plant may have beneficialeffects in the prevention and treatment of dyslipidemias and hyperglycemia.
Obesity is considered an important risk factor for several disorders, such as diabetes mellitus, systemic arterial hypertension, dyslipidemia, and atherosclerosis, which are associated with inflammation and oxidative stress as a trigger factor. Passiflora edulis contains important bioactive compounds, such as phenolics, carotenoids, vitamin C, and polyamines in pulp, leaves, seeds, and bark. Aim: To evaluate the effect of bark of Passiflora edulis (BPe) on body composition, and metabolic and oxidative stress parameters in genetically obese mice. Methods: Obese male db/db mice (n = 14 animals) received normal feeds and water ad libitum for 8 weeks. Then, animals were randomly divided to continue either receiving standard chow (obese, n = 7 (OB)) or feed with standard chow plus bark Passiflora edulis (BPe) (obese + BPe, n = 7 (OB + BPe)) for 8 more weeks, totaling 16 weeks. BPe was added to chow (7 g of BPe/kg of chow corresponding to 1.5 g/kg of body weight). The parameters evaluated in animals included food and caloric intake, body weight, body fat, plasma glucose, Triglycerides, and total cholesterol. Malondialdehyde and antioxidant capacity were evaluated in plasma and organs. Groups were compared by Student t-test, with p < 0.05. Results: BPe reduced visceral and subcutaneous fat deposit and adiposity index, cholesterol and Triglyceride levels, ameliorated the antioxidant capacity, and reduced malondialdehyde (MDA) levels. Conclusion: the bark of Passiflora edulis was effective in improving body composition, and metabolic and antioxidant parameters in obese mice.
Flour made from Passiflora edulis fruit peel has been used in Brazil to treat diabetes. This study evaluated the effects of pectin from P. edulis on rats with alloxan-induced diabetes, on myeloperoxidase release from human neutrophils, and on carrageenan-induced paw edema. In the experiments on carrageenan-induced paw edema, paws were dissected for hematoxylin–eosin staining and immunohistochemistry determinations of tumor necrosis factor-α and inducible nitric oxide synthase. Male Wistar rats were divided into the following groups: diabetic controls and diabetic treated with pectin daily for 5 days (0.5–25 mg/kg orally). Glibenclamide and metformin were used as reference drugs. Forty-eight hours after alloxan administration, blood measures were determined (before treatment) and again 5 days later (after treatment). Pectin decreased blood glucose and Triglyceride levels in diabetic rats. Pectin also decreased edema volume and release of myeloperoxidase (0.1–100 μg/mL). It also significantly decreased neutrophil infiltration and partially decreased immunostaining for tumor necrosis factor-α and inducible nitric oxide synthase. In conclusion, these data indicated that pectin, a bioactive compound present in P. edulis, has potential as a useful alternative treatment for type 2 diabetes. Its anti-inflammatory properties are probably involved in its antidiabetic action.
The Effects of Passiflora Edulis Sims’s Seed Extract on Total Cholesterol in Atherogenic Young Rats
Purple passion fruit (Passiflora edulis Sims) is one of antioxidant that contain flavonoid, as a protection atherosclerosis process. Its juice has been proof to reduced total cholesterol, but its seed also has been predicted to reduce it. The objective was to find the effects of Passiflora edulis Sims’s seed extract in different doses in affecting lipid profile serum level in young rats (Rattus novergicus) in fourteen days. There were four groups containing 20 male rats which were devided into: normal diet group (C0); atherogenic diet group (C1); atherogenic diet and 50mg/kg body weight (P1); atherogenic diet and 100mg/kg body weight (P2). Results of this study were there was significant difference of body weight, total cholesterol, and Triglyceride, but not for low and high density lipoprotein serum level. The result reported that body weight showed significant difference between C0, C1, P1, and P2. Total cholesterol serum between C0 and C1 group (p=0.04), also between C1 and P2 (p=0.003). There was also significant difference of Triglyceride serum level between C0 and P1 (p=0.04) and C0 and P2 (p= 0.03). Based on these results it can be concluded that Passiflora edulis Sims’s seed extract has potential effect in lowering total cholesterol and Triglyceride serum in young rats.
Persea americana Mill
cholesterol-lowering Activity of Persea americana Mill
Several plant extracts were screened for their 3-hydroxy-3-methylglutaryl coenzyme A reduc- taseInhibitory activity. Persea americana Mill. was one of the most active extracts. The bioactive compo- nent was identified using bioassay-guided scheme through the use of various chromatographic techniques. Quercitrin and afzelin were identified using LC-MS techniques.
Avocados are characterized by their high dietary fiber and unsaturated fatty acids content. This study aimed to evaluate the hypolipidemic and hypocholesterolemic effect of avocado Hass on hamsters fed with diets based on freeze-dried pulp avocado (FAD) and defatted paste avocado (DPAD). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), serum Triglycerides (TG), and atherogenic index of plasma (AIP) were evaluated along with total lipids in liver and feces. Compared to the control diet, FAD and DPAD reduced the serum TG levels by 76.47 and 46.06%, respectively. FAD also reduced the serum TC levels by 16.39%. FAD and DPAD decreased the lipids in the liver by 33.61% and 10.0% and the amount of lipid excreted in feces by 73.47% and 41.50%, respectively. FAD showed the lowest AIP, 0.60, compared to that of DPAD and the control, 1.83 and 1.94, respectively. Freeze-dried avocado pulp was found to be efficient in reducing dyslipidemia values in hamsters.
Hypolipidemic Effect of Avocado Peel (Persea americana Mill.) Extract in Rats with Dyslipidemia
Dyslipidemia is a disorder of lipid metabolism and one of the modifiable risk factors for cardiovascular disease. The prevalence of dyslipidemia based on raised total cholesterol in the world was 39%, of which 37% for men and 40% for women. Cholesterol-lowering drugs have been reported to have many side effects. One alternative medicine in reducing blood cholesterol levels by utilizing the potential of the avocado peel. This research was experimental with a pre-posttest control group design. This research was used 30 Sprague Dawley male rats divided into 6 groups, namely the normal control group (CG1), negative control (CG2), positive control (CG3) and 3 treatment groups (TG) who received avocado peel extract (APE) at 75, 150, and 300 mg/200gr bodyweight rats. Data were tested using a one-way ANOVA. The results showed that APE significantly reduced the levels of LDL-C (P<0.05) was 17.82±2.62, 29.62±2.00, and 36.33±4.47 mg/dl (TG1, TG2, TG3). Decreased Triglycerides levels (P<0.05) of 1.62±4.17, 14.05±5.16, and 29.67±5.79 mg/dl (TG1, TG2, TG3). The increased levels of HDL-C (P<0.05) were 29.67±5.79, 22.63±4.82, and 34.35±2.72 mg/dl (TG1, TG2, TG3). Avocado peel (Persea americana Mill.) extract showed a hypolipidemic effect by reducing LDL-C, Triglycerides, and increasing HDL-C levels in rats with dyslipidemia.
Male Sprague Dawley rats were divided into four groups: groups 1 and 2 were fed normal rat chow (5% fat) and groups 3 and 4 were fed HFD (23% fat) for a period of 14 weeks. In addition, groups 2 and 4 rats were administered orally with 100 mg/kg body weight of HAEPA from third week. After 14 weeks, rats were sacrificed, and serum/plasma levels of total cholesterol, phospholipids, Triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and adiponectin were determined. The mRNA expression of adiponectin, PPAR-γ and protein expression of PPAR-γ were also evaluated.
Persimmon tannin
The purpose of this study was to investigate whether persimmon tannin is associated withcholesterolefflux and macrophage-reversecholesteroltransport (RCT). In J774A.1 macrophage cells, persimmon tannin could inhibit cellularcholesterol accumulation and promote 22-NBD-cholesterolefflux through inhibiting the phosphorylation of ERK1/2 and up-regulating the protein levels of PPARγ. Macrophage RCT in vivo was evaluated by injecting 22-NBD-cholesterol-loaded J774A.1 macrophages intraperitoneally into C57BL/6J mice. Administration of persimmon tannin significantly (P < 0.05) decreased thecholesterol concentration in bothserum and liver, and increased faecalcholesterol excretion compared with thehigh-cholesterol group. In transcriptional levels, persimmon tannin enhanced the expression ofcholesteroltransport-related genes (ABCA1, LCAT, ABCG5/G8, NPC1L1 and CYP7A1) and their upstream nuclear receptors (PPARγ, PPARα and LXRα). Moreover, the regulation of persimmon tannin on RCT-related genes might be mediated by its inhibition on ERK1/2 in mice. Therefore, persimmon tannin promoted macrophagereversecholesteroltransport through the regulation on ERK1/2-PPARγ signaling pathway both in vitro and in vivo.
Phaseolus vulgaris Linn extract
Thecholesterol-lowering property of beans has been shown in several studies. The propose of the present work was to investigate theeffect of black beans (Phaseolus vulgaris, L.) without hulls onbloodcholesterol of hypercholesterolemic rats. Four groups of 8 male rats, Wistar strain, initial body weight of 200 g were kept at +/- 25 degrees C in a light-dark cycle of 12 h, for 28 days. The group Standard received a basal caseindiet. Group Control received the basaldiet added of 1%cholesterol plus 0.1% cholic acid. The group BB received adiet similar to the Control, substituted by 30% black beans, on dry-weight. The group SBB received black beans without hulls, equivalent to 30% of whole beans. The addition ofcholesterol and cholic acid raisedbloodcholesterol levels of rats on Controldiet by 58%, in relation to the Standard. BBdiet reducedbloodcholesterol by 15% (non-significant-NS) and SBBdiet reduced (p < 0.05) by 35%, in relation to the Controldiet. The levels of HDL-cholesterol were reduced (p < 0.05) by both beandiets. SBBdiet promoted ahigher excretion of fecalcholesterol, compared to the Control. This suggests that beans without hulls promote ahighercholesterol output and that the whole beans, although had loweredbloodcholesterol (NS), kept it in the enterohepatic circulation. Thehypocholesterolemic compounds of beans seem to be located in the inner part of the grain. Further studies are necessary to identify these compounds and to elucidate their mechanisms of action.
Phellinus baumii
PBE was administered daily by oral gavage for 12 weeks. Oral administration of PBE (500 mg/kg) significantly reduced body weight gain, hepatic lipid concentrations, and fat accumulation in epididymal adipocytes compared with mice fed HFD alone (P < .05). mRNA expression of genes related to Triglyceride (TG) synthesis was suppressed in the PBE groups, and fatty acid synthase activity was also significantly inhibited (P < .05). Furthermore, we evaluated the effect of PBE on TG absorption and detected marked reduction in TG absorption in Xenical- and PBE-treated mice compared with the control group (P < .05). To determine the active compound of PBE, fractionation was conducted, and interfungin A, davallialactone, and hypholomine B were identified as the main compounds. Among the three identified compounds, as a representative compound, davallialactone was also shown to suppress fat accumulation in an in vitro model system. These anti-obesity and hypolipidemic effects appear to be partly mediated by suppressing plasma and hepatic fat accumulation through the inhibition of enzymes associated with hepatic and intestinal lipid absorption and synthesis.
Phyllantus emblica
The effect of aqueous fruit extract of Phyllanthus emblica Linn was studied on type-II diabetes,Triglycerides (TG) and liver-specific enzyme, alanine transaminase (ALT). Our study showed that aqueousfruit extract, in a dose of 200mg/kg body weight, significantly decreased the blood glucose level after its intra-peritoneal administration in alloxan-induced diabetic rats (p<0.05). Almost similar decreased in glucose levelwas also observed by chlorpropamide, a known antidiabetic drug in a dose of 84 mg/kg. The aqueous extractalso induced hypoTriglyceridemia by decreasing TG levels at 0, 1, 2 and 4 hours in diabetic rats (p<0.05). Inaddition, the extract was also found to improve liver function by normalizing the activity of liver-specific enzymealanine transaminase (ALT).
Pinellia ternata(Thunb) Breit.)extract
Context: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) (PT) has been widely used in the treatment ofAtherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood.
Objective: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia.
Materials and methods: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups (n = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT+LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT) and endothelial progenitor cells (EPCs) (with injection of 5 × 105/cells), and treated for 4 or 8 weeks.
Results: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL+/FITC-UEA-1+ population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in theblood, decreased TCHO, TG,LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in theblood. However, these changes werereversed by the PI3K/Akt pathwayInhibitor LY294002.
Discussion and conclusions: PT can be developed as anAtherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on theeffects of PT on intimal hyperplasia in wire-injuredAtherosclerosis patients and explore in depth some other relevant molecular mechanisms.
Platycodon grandiflorus (Jacq.)A.DC. extract
Platycodin D enhancesLDLR expression andLDL uptake via down-regulation of IDOL mRNA in hepatic cells
The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancereffects. A previous study showed that PD hadcholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of theLDLR (IDOL) mRNA, leading to the enhanced uptake ofLDL-derivedcholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life ofLDLR protein byreducing IDOL-mediatedLDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergisticeffects on the improvement ofLDLR expression andLDL-C uptake. Together, these results provide the first molecular evidence for anti- hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.
The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidationeffects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by ahigh-fatdiet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chowdiet or a HFD, either supplemented with or without PG, for 16 weeks.serumlipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PGameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, andimproved insulin sensitivity by regulating the PI3K/Akt/GSK3β signaling pathway. Our data showed thatdietary PG have profoundeffects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD.
cholesterol-loweringeffect of platycodin D in hypercholesterolemic ICR mice
This study investigates the in vivohypocholesterolemic action of platycodin D and its in vitro evidence for thecholesterol-lowering properties. In order to examine theeffects of platycodin D on hypercholesterolemia in male ICR mice, platycodin D with doses of 15, 30 or 50 mg/kg was orally administered for 8 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of Triglyceride and different types ofcholesterol in theserum, livers and feces were determined. Theeffects of platycodin D oncholesterolmetabolism were further investigated with several in vitro assays, including antioxidanteffect on low density lipoprotein oxidation, inhibition of human acyl-coenzyme A:cholesterol acyltransferase (hACAT) andserum lipoprotein associated-phospholipase A2 (Lp-PLA2), as well as the regulation of farnesoid X receptor. The formation of insoluble complex between platycodin D andcholesterol was also investigated. Following an eight week experimental period, the body weights of platycodin D-fed mice were less than those of control mice on ahighcholesteroldiet by 11.2 ± 5% (P < 0.01) with 15 mg/kg platycodin D, 11.7 ± 5% (P < 0.01) with 30 mg/kg platycodin D, and 23.4 ± 7.9% (P < 0.0001) with 50 mg/kg platycodin D, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Triglyceride andcholesterol concentrations were decreased inserums and livers, but increased in feces. Some of the in vitro observations revealed that thehypocholesterolemiceffect of platycodin D is partly associated with inhibition to hACAT activity and antagonism to the farnesoid X receptor as well as the formation of insoluble complex with between platycodin D andcholesterol. Both in vivo and in vitro results demonstrate a potential value of platycodin D as a novelcholesterol-lowering and anti-atherogenic candidate.
Obesity is caused by an energy imbalance between food intake and energy expenditure, and has detrimental effects on human health. Platycodon (Platycodon grandiflorum) widely grows in Korea, Japan, and China. It has long been used for food and as a medicinal product. However, the mechanism of the improvement of obesity by platycodon was still not clear. Therefore, we investigated the detailed mechanisms of the antiobesity activity of platycodon extracts. Twenty mice (C57BL/6J) were placed into five groups. The test group received 1 g/kg platycodon extracts. The positive control group received 10 mg/kg orlistat, while the negative control and normal control groups received phosphate-buffered saline. The extracts were given orally daily for 8 weeks. The in vivo treatment of platycodon extracts reduced body weight gain by 7.5%, improved plasma lipid profiles. In the groups given platycodon extracts, leptin was significantly decreased whereas adiponectin was increased. Furthermore, platycodon extracts downregulated lipogenic gene (e.g., lipoprotein lipase, acetyl-CoA carboxylase, and fatty acid synthase) expression and increased lipolysis genes (e.g., carnitine palmitoyltransferase 1α, hormone-sensitive lipase, and uncoupling proteins 2) in liver and white adipose tissue. In addition, platycodon extracts inhibited the expression of key adipogenic transcriptional factors. In conclusion, we have demonstrated that platycodon extracts ameliorate high-fat diet-induced obesity and its related metabolic disease by regulating multiple pathways. Dietary supplementation of platycodon extracts as a functional food and medicinal ingredients may be suitable for prevention and treatment of obesity.
We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract (PGEA) would help reduce the vascular cell injury caused by oxidized low-density lipoprotein (oxLDL) and prevent high-fat (HF) diet–induced dyslipidemia and oxidative stress by up-regulating antioxidant proteins. We investigated the protective effects of PGEA against vascular endothelial cell injury induced by oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these effects were studied. The protective effects of PGEA were investigated with respect to calf pulmonary arterial endothelial (CPAE) cell viability and the lactate dehydrogenase release during oxLDL treatment.
Platycodon grandiflorum (PG) is a perennial plant from the Campanulaceae family, well known as a traditional herbal medicine for the treatment of asthma, diabetes, and respiratory disorders. It contains diverse bioactive compounds such as triterpenoid saponins, flavonoids, polyphenols, and fibers [1,2,3]. PG also possesses antioxidant, anticancer, anti-inflammatory, and hepato-protective pproperties [4,5,6]. Furthermore, many researchers have reported on the anti-obesity effect of PG and its constituents through the reduction of total cholesterol (TC) and Triglyceride (TG) levels, and the inhibition of pancreatic lipase activity.
Adipocytes regulate lipid metabolism according to physiological energy requirements. A dysfunctional lipid metabolism can lead to obesity and its complications such as hepatic steatosis, diabetes, and hyperlipidemia. In our study, the impact of Platycodon grandiflorus root ethanol extract (PGH) on lipid excretion and thermogenesis-related markers in diet-induced obesity mice was analyzed. Our data show that PGH elevated fatty acid uptake in epididymal adipose tissue by increasing Cd36, Slc27a1, Ffar2, and Ffar4 expression, which led to decreased blood free fatty acid concentrations. Moreover, PGH normalized body weight and fat mass in diet-induced obese mice by increasing lipolysis (Plin1, ATGl, and Hsl) and fatty acid oxidation. Changes in the levels of browning-related genes, enzyme activity of carnitine palmitoyltransferase, and the overall transcriptome (Bmp4, Cidec, Ucp3, Sirt3, and Cox4i1) led to promote brown adipose tissue-like features (browning) in epididymal white adipose tissue and enhanced energy expenditure. Our results suggest that PGH promotes lipid excretion and thermogenic function in high-fat diet-induced obese mice, which are mediated by regulation of fat metabolism.
The effects of FPG on HFD-induced obesity were primarily responsible for inhibiting adipogenesis in adipose tissue and regulating lipid metabolism, such as through lipogenesis and fatty acid oxidation. Additionally, FPG ameliorated serum total cholesterol, Triglyceride, and low-density lipoprotein cholesterol levels. Hence, FPG may be an alternative treatment for controlling obesity through downregulating lipid accumulation.
Pleurotus ostreatus extract
lipid lowering effects of oyster mushroom (Pleurotus ostreatus) in humans
Elevatedcholesterol and triacylglycerol levels are known risk factors for cardiovascular diseases. A number of animal studies have indicated that the consumption of oyster mushrooms (Pleurotus ostreatus) can positively influence thelipid profile. The present intervention study for the first time investigated thecholesterollowering properties of an oyster mushroomdiet in humans. A total of 20 subjects (9 male, 11 female; 20–34 years) were randomized to take either one portion of soup containing 30 g dried oyster mushrooms or a tomato soup as a placebo on a daily basis for 21 days. Standardizedblood concentrations oflipid parameters andoxidized low density lipoprotein were measured at the baseline (t0) and after 21 days (t21). Treatment with oyster mushroom soup decreased triacylglycerol concentrations (−0.44 mmol/L; p = 0.015) andoxidized low density lipoprotein levels (−7.2 U/mL; p = 0.013) significantly, and showed a significant tendency inlowering totalcholesterol values (−0.47 mmol/L; p = 0.059). Noeffects on low density lipoprotein andhigh density lipoprotein levels were found. The beneficialeffects of oyster mushroom onbloodserum parameters may be attributed to the presence of linoleic acid, ergosterol and ergosta-derivatives which showed notable activity in oxygen radical absorbance capacity and cyclooxygenase inhibition assays in vitro.
hypolipidemic Activities ofdietary Pleurotus ostreatus in hypercholesterolemic Rats
This work was conducted to investigatedietary supplementation of oyster mushroom fruiting bodies on biochemical and histological changes in hyper and normocholesterolemic rats. Six-week old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Feeding adiet containing a 5% powder of Pleurotus ostreatus fruiting bodies to hypercholesterolemic rats reduced plasma totalcholesterol, Triglyceride , low-density lipoprotein (LDL), totallipid, phospholipids, andLDL/high-density lipoprotein ratio by 30.18, 52.75, 59.62, 34.15, 23.89, and 50%, respectively. Feeding oyster mushrooms also significantly reduced body weight in hypercholesterolemic rats. However, it had no adverseeffects on plasma albumin, total bilirubin, direct bilirubin, creatinin,blood urea nitrogen, uric acid,glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, or enzyme profiles. Feeding mushroom increased totallipid andcholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that P. ostreatus significantly reduced plasma β and pre-β-lipoprotein but increased α-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining revealed normal findings for mushroom-fed hypercholesterolemic rats. These results suggest that a 5% P. ostreatusdiet supplement provided health benefits by acting on the atherogeniclipid profile in hypercholesterolemic rats.
We studied theeffect of the edible mushroom Pleurotus ostreatus (4% indiet containing 1 % ofcholesterol) onserum and liverlipids in female rats with hereditary enhanced sensitivity to alimentarycholesterol. We found that the consumption of the mushroom-containingdiet preventedserumcholesterol increase which was manifested at the end of the 4th week of the experiment. At the end of the 7th week of the experiment the choles-terolemia was lowered by almost 40% as compared with control animals kept on the samediet but without the mushroom. The decrease inserumcholesterol levels is a consequence of the decreasedcholesterol concentrations of very-low-density lipoproteins and of low-density lipoproteins.
Lipid lowering effects of oyster mushroom (Pleurotus ostreatus) in humans
Consumption of oyster mushrooms lowers concentrations of Triglycerides, cholesterol and oxidized LDL. Bioactive compounds identified in oyster mushrooms. Contents of oyster mushrooms showed antioxidative and cyclooxygenase inhibition properties.
Hypolipidemic Activities of Dietary Pleurotus ostreatus in Hypercholesterolemic Rats
This work was conducted to investigate dietary supplementation of oyster mushroom fruiting bodies on biochemical and histological changes in hyper and normocholesterolemic rats. Six-week old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Feeding a diet containing a 5% powder of Pleurotus ostreatus fruiting bodies to hypercholesterolemic rats reduced plasma total cholesterol, Triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and LDL/high-density lipoprotein ratio by 30.18, 52.75, 59.62, 34.15, 23.89, and 50%, respectively.
Nutritional, Anti-nutritional and Biochemical Studies on the Oyster Mushroom, Pleurotus ostreatus
Nutritional, anti-nutritional and biochemical studies on the Oyster mushroom, Pleurotus ostreatus using Wistar albino rats were evaluated. Nutritional compositions such as protein, crude fats, fatty acids, vitamins A, B complex, C, and K; as well as potassium, sodium, calcium, zinc, copper and manganese minerals with high calcium-phosphorus ratio and amino acids were observed in Oyster mushroom, P. ostreatus. Saponins, alkaloids, oxalate, tannins and phytate were among the anti-nutrients observed in the studied sample.
Policosanol
cholesterol-lowering effects of policosanol in rabbits.
Policosanol is a natural mixture ofhigher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced totalcholesterol and low density lipoproteincholesterol (LDL-C)serum levels in a dose dependent manner.serum Triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent.high density lipoproteincholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in totalcholesterol values induced by policosanol is mainly mediated through a decrease inLDL-C levels.
Theeffect of policosanol, a mixture ofhigh-molecular-weight aliphatic alcohols isolated from sugar-cane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50mg/kg) the increases in plasma totalcholesterol andLDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepaticcholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125l-labelledLDL fromserum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t½) was significantly decreased after policosanol treatment. The hepaticLDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake ofLDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasmaLDL-C in rabbits fed on a wheat starch-caseindiet byreducingcholesterol biosynthesis in the liver. Such aneffect could account for the enhancement ofLDL catabolism through the receptor-mediated pathway.
Antiatherosclerotic Efficacy of Policosanol, Red Yeast Rice Extract and Astaxanthin in the Rabbit
Theeffects of policosanol (P), of extract of red yeast rice (rice fermented with Monascus purpureus) (RYE) and of astax-anthin (A) (constituents of Armolipid®) were investigated in a model of experimentalAtherosclerosis provoked in the rabbit by atherogeniccholesterol-enriched feed (ACEF). P and RYE and their combination were able to lower the increase ofserum totalcholesterol and ofLDLcholesterol elicited by 3-month feeding with ACEF. They also were able to reduce the increase ofblood malondial-dehyde (MDA), a tracer oflipid peroxidation by the free radicals released by ACEF. When combined, the substances developed either additive or potentiatedeffects, supporting the rationale of their combination. Remarkable was the protectiveeffect onlipid infiltration in the aortic wall provoked by ACEF, which was reduced by P and by RYE and almost completely prevented by the addition of A to the P-RYE combination.
Moisture content of facial skin increased up to 38 and 18% from initial levels in the YS and MN groups, respectively. Serum Triglyceride (TG) levels decreased to 28 and 26% from initial levels in the YN and MN groups, respectively. The percentage of high-density lipoprotein-cholesterol (HDL-C) in total cholesterol was elevated in all subjects (YN, 36%; YS, 35%; MN, 8%) after 8 weeks of policosanol consumption.
The effects of policosanol on Triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol.
In the policosanol group, plasma total cholesterol (TC) and Triglyceride (TG) levels were reduced up to 20% and 14%, respectively, and HDL-C level was elevated up to 1.3-fold compared to that at week 0. TG/HDL-C and cholesteryl ester transfer protein (CETP) activities were reduced up to 36% and 20%, respectively.
Polydatin
Studies have shown that polydatin decreased serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), Triglycerides (TG), hepatic TG concentrations, and LDL-C/high-density lipoprotein cholesterol (HDL-C) and TC/HDL-C ratios. These effects may indicate the protective effect of polydatin on the liver, coronary heart disease, and atherosclerosis [125,126,127]. Oxidative stress caused by the proliferation of vascular smooth muscle cells (VSMCs) leads to plaque formation and the progression of atherosclerosis. Polydatin inhibited oxidative stress by activating the NOS/Sirt1 pathway [115]. Polydatin also exerted potential protective effects against atherosclerosis by regulating pre-B-cell colony-enhancing factor (PBEF) and the inhibition of cholesterol accumulation in PBEF-induced macrophages.
Polygonum cuspidatum
Resveratrol (Res) was previously reported to be capable oflowering plasma TC andLDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have aneffect on bile acidmetabolism in the liver: a significant way in eliminatingcholesterol from the body. As one of the major metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol-lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity inlowering cellular TC content. The presence of Res and Gres caused a significant increase in hepatic CYP7A1 and BSEP, indicating the increase in the synthesis andefflux of bile acids, respectively. The reduction of HMG-CoAR tied to a decrease in de novo synthesis ofcholesterol and the increase of ABCG5 suggested the increase of directefflux ofcholesterol. All above variations reduced the hepaticcholesterol level, which triggered the significant enhancement ofLDLR, illustrating the improvement of clearance ofLDL-C from the plasma and prevention ofAtherosclerosis. Overall, this study demonstrated both Res and Gres might have capabilities inlowering hepaticcholesterol through increasing in the synthesis andefflux of bile acids, and decreasing in synthesis and increasing in theefflux ofcholesterol. Gres would have preferred potential than Res because of its lower cytotoxicity, which indicated that the action of the metabolites should also be considered in the future studies.
Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemiceffect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) couldameliorate thebloodlipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors were significantly enriched. Furthermore, in vitro experiments were performed to determine thelipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze theeffects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemiceffects.
Polygonatum odoratum extract
In the preventive experiment, the ER blocked body weight gain, and lowered serum total cholesterol (TC), Triglyceride (TG) and fasting blood glucose, improved glucose tolerance test (GTT) and insulin tolerance test (ITT), reduced the levels of serum insulin and leptin, and increased serum adiponectin levels in mice fed with a high-fat diet significantly. In the therapeutic study, we induced obesity in the mice and treated the obese mice with ER for two weeks. We found that ER treatments reduced serum TG and fasting blood glucose, and improved glucose tolerance in the mice. Gene expression analysis showed that ER increased the mRNA levels of peroxisome proliferator-activated receptors (PPAR) γ and α and their downstream target genes in mice livers, adipose tissues and HepG2 cells. Our data suggest that ER ameliorates metabolic disorders and enhances the mRNA expression of PPARs in obese C57BL/6 mice induced by high-fat diet.
Polygonum multi forum Thunb.root extract
Review of clinical studies of Polygonum multiflorum Thunb. and its isolated bioactive compounds
Polygonum multiflorum Thunb. (PMT), officially listed in the Chinese Pharmacopoeia, is one of the most popular perennial Chinese traditional medicines known as He shou wu in China and East Asia, and as Fo-ti in North America. Mounting pharmacological studies have stressed out its key benefice for the treatment of various diseases and medical conditions such as liver injury, cancer, diabetes, alopecia,Atherosclerosis, and neurodegenerative diseases as well. International databases such as PubMed/Medline, Science citation Index and Google Scholar were searched for clinical studies recently published on P. multiflorum. Various clinical studies published articles were retrieved, providing information relevant to pharmacokinetics-pharmacodynamics analysis, sleep disorders, dyslipidemia treatment, and neurodegenerative diseases. This review is an effort to update the clinical picture of investigations ever carried on PMT and/or its isolated bio-compounds and to enlighten its therapeutic assessment.
Experiments have shown that the root of Polygonum multiflorum exhibits inhibitory effect on Triglyceride (TG) accumulation in the liver of mice induced by CCl4, cortisone acetate and thioacetamide (TAA). Its processed products (I, II) were found to be effective in lowering the accumulated TG induced by cortisone acetate. The root of Polygonum multiflorum and its processed products also reduced the enlargement of liver by CCl4.
Polymnia Sonchifolia Poepp.
This study was carried out to investigate theeffect of Yacon (Polymnia sonchifolia Poepp. & Endl.) powder oncholesterol-lowering and anti-obesityeffects in rats fed ahigh fat-highcholesteroldiet for 4 weeks to induce hyperlipidemic and obese rat model. Weight-matched male Sprague-Dawley rats were assigned to four groups according todietary fat,cholesterol levels and Yacon powder levels. Experimental groups were normaldiet group (N),high fat-highcholesteroldiet group (HFC),high fat-highcholesteroldiet with 5% Yacon powder group (HFC-PSL) andhigh fat-highcholesteroldiet with 10% Yacon powder group (HFC-PSH). The body weight gain and FER were increased by ahigh fat-highcholesteroldiet, but gradually decreased in the Yacon powder fed groups compared with the HFC group. Food intake was lower in HFC groups compared with N group. The liver and adipose tissue weights of HFC group were heavier than those of N group, whereas those of groups administered Yacon powder were gradually decreased. Theserum ALT, AST, ALP and LDH activities elevated by ahigh fat-highcholesteroldiet were significantly decreased by Yacon powder administration. Levels ofserum totalcholesterol,LDL-cholesterol, atherogenic index and cardiac risk factor showed a decreasing tendency in the Yacon powder fed groups compared with HFC group. Theserum HDL-cholesterol level decreased in the HFC group and markedly increased in the Yacon powder fed groups. Levels of totalcholesterol and Triglyceride in liver and adipose tissues were lower in Yacon powder administered groups than those in HFC group. These results suggest that Yacon powder may improvelipidmetabolism ofserum, liver, and adipose tissue and potentially reducelipid storage.
Pomegranate (Punica granatum L.)
Pomegranate (Punica granatum L.) will be examined by looking at the ability between pomegranate extracts or fractions, which are moreeffective inlowering totalbloodcholesterol and Triglyceride levels in mice. This study aims to determine the active pomegranate fraction that can reduce the totalcholesterol levels and Triglyceride in mice. The research method used was an experimental method with a Completely Randomized Design (CRD) which was divided into 6 treatment groups, and test animals divided into 6 treatment groups namely negative control given aquades, positive control fed ahigh-fatdiet, given simvastatin, given 25 mg/grBB of pomegranate methanol fraction, given 50 mg/grBB of pomegranate methanol fraction, given 100 mg/grBB of pomegranate methanol fraction, each treatment group will be divided into 4 male mice.Based on the results of this study that the active fraction that has aneffect inreducingbloodcholesterol levels and mice Triglycerides is the treatment given 100mg/grBB of pomegranate water methanol fraction.
This work is aimed to evaluate phenolics composition, and in vitro antioxidant activities of hydro-methanol pomegranate (Punica granatum L.) peel extract (MPE). In addition, the antihyperglycemic, hypolipidemic, and hepatoprotective effect of MPE in Wister albino rats was compared with standard drugs (glibenclamide and atorvastatin). Total phenolic content and total flavonoid contents in MPE (mg g−1) accounted for 188.9 as GAE and 13.95 as QE, respectively.
After supplementation with MiPo, the incremental area under the curve of Triglycerides decreased to half of the initial values. The HDL distribution shifted from large HDL to intermediate and small-size particles during the postprandial period in the basal conditions, whereas such a shift was no longer observed after MiPo supplementation. Consistently, HDL isolated from postprandial plasma samples hindered the vasodilation of aorta rings, and this endothelial dysfunction was reverted after MiPo consumption. (4) Conclusions: MiPo exhibited the same beneficial effects on the lipid profile and PON1 activity as the previously reported fresh pomegranate.
Pomegranate was associated with a reduction in the total cholesterol (p ˂ .001), Triglyceride (p ˂ .001), low-density lipoprotein cholesterol (LDL-C)-to-high-density lipoprotein cholesterol (HDL-C) ratio (p ˂ .003), fasting blood sugar (p ˂ .001), homeostatic model assessment of insulin resistance (p = .02), diastolic blood pressure (p = .04), weight (p ˂ .001), body mass index (p ˂ .001), and waist circumference (p = .002), as compared to placebo. A significant increase was observed in serum HDL-C (p ˂ .001) after intervention with the pomegranate extract. However, no significant difference was shown between the two groups in serum insulin and LDL-C.
Thirty eight obese women (30< body mass index (BMI) >35 kg/m2) with dyslipidemia were allocated into two groups receiving two 500 mg pomegranate peel extract (n = 19) or placebo (n = 19) daily for 8 weeks. Serum lipid profile (total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), Triglycerides (TG)), Blood Pressure(BP), serum high sensitive-C reactive protein (hs-CRP) and BMIwere measured.
Primitivo polyphenolic extract
Purpose
The aim of the study was to evaluate the vascular anti-inflammatoryeffects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action.
Methods
Human endothelial cells were incubated with increasing concentrations (1–50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1–25 μmol/L), including hydroxycinnamic acids (p-coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes (trans-resveratrol, trans-piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial–monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1.
Results
Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress.
Conclusions
This study showed multiple anti-inflammatory andAnti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases includingAtherosclerosis.
Propolis extract
The ethanolic extract of propolis (EEP) is beneficial in increasinghigh density lipoprotein (HDL)cholesterol (HDL-C) and diminishing risks ofAtherosclerosis. In this study, we examined theeffects of EEP onreversecholesteroltransport in mice. 3H -cholesterol laden macrophage was injected intraperitoneally into mice fed by gastric gavage with EEP. Plasmalipid level was determined and 3H-cholesterol was traced in plasma, liver and feces. Theeffects of EEP on ATP-binding cassettetransporter A1 and G1 (ABCA1 and ABCG1) and scavenger receptor BI (SR-BI) in mice liver and in cultured cells were also investigated. EEP administration led to a significant increase in HDL-C and peritoneal macrophage-original 3H-cholesterol in plasma, liver and feces. Liver protein expressions of ABCA1 and ABCG1 were increased but SR-B1 was not. In vitro experiments with HepG2 and Raw264.7 cell lines confirmed the above results. The finding of these studies shows that EEP-enhancedreversecholesteroltransport may have resulted from EEP stimulated plasma HDL level and hepatic ABCA1 and ABCG1 expression.
The level of PPARγ protein in the adipose tissues of the high group was significantly lower than that of the control group. In plasma and the liver, the high group showed a significantly reduced level of cholesterol and Triglyceride compared to the control group. The liver PPARα protein level of the high group was significantly higher than that of the control group. The liver HMG-CoA reductase protein in the high group was also significantly lower than that in the control group. Results from rats on an olive oil loading test were used to investigate whether propolis inhibited Triglyceride absorption.
The aim of meta-analysis was to assess the effects of propolis on markers of oxidative stress, lipid profiles, inflammation and glycemic control, liver enzymes, and weight control. The heterogeneity between the included studies was indicated using the Cochrane’s Q test and I-square (I2) statistic. 14 trials were included in this meta-analysis. Our meta-analysis indicated a significant reduction in fating glucose (WMD: -17.00; 95% CI: −30.88, −3.11), HbA1C (WMD: -0.42; 95% CI: −0.75, −0.10), and insulin (WMD: -1.75; 95% CI: −3.24, −0.26) and a marginally significant reduction in insulin resistance (WMD: -0.60; 95% CI: −1.20, 0.00) following propolis supplementation in 10, 8, 6, and 5 studies, respectively.
Prosopis cineraria bark
dietary antioxidants and flavonoids like phytochemicals occurred in several herbs have potential to improve cardiovascular health. Prosopis cineraria (Fabaceae) is also widely uses on above basis for traditional therapeutic purposes. It is the Thar Desert prominent tree. This study evaluated thehypolipidemic andAntiatheroscleroticeffects of Prosopis cineraria bark extract in hyperlipidemic rabbits. The rabbits were made to induce exogenously hyperlipidemic through orally administration ofhigh fatdiet andcholesterol powder (500mg/Kg body weight per day in 5 ml of coconut oil orally for 15 days). The induced hyperlipidemic rabbits were treated comparatively by bark extract of Prosopis cineraria and standard drug. The administration of Prosopis cineraria bark extract (70% ethanol) significantly (P ≤ 0.001) reducedserum totalcholesterol (88%),LDL-C (95%), Triglyceride (59%), VLDL-C (60%) and also ischemic indices (Totalcholesterol/LDL-C andLDL-C/HDL-C). The Prosopis cineraria bark extract also significantly (P ≤ 0.001) prevented the atherogenic changes in aorta. Toxicity profile parameters were also examined and remained under normal ranges. Results indicated that Prosopis cineraria bark hashypolipidemic andAntiatherosclerotic efficacy along with non-toxic nature.
Antihyperglycemic, antihyperlipidemic and antioxidative potential of Prosopis cineraria bark
Alloxan administration in male Swiss albino mice, induced diabetes by increasing blood glucose concentration and reducing hepatic glycogen content as compared to normal control group. Besides, serum lipid profile parameters such as total-cholesterol, Triglyceride, low-density lipoprotein and very low-density lipoprotein-cholesterol were also elevated, whereas, the level of high-density lipoprotein-cholesterol was reduced significantly (P<0.05) in diabetic mice. Treatment of diabetic animals with crude ethanolic extract of bark of Prosopis cineraria (P. cineraria) for 45 days, significantly lowered blood glucose level, elevated hepatic glycogen content and maintained body weight and lipid-profile parameters towards near normal range.
The administration of Prosopis cineraria bark extract (70% ethanol) significantly (P ≤ 0.001) reduced serum total cholesterol (88%), LDL-C (95%), Triglyceride (59%), VLDL-C (60%) and also ischemic indices (Total cholesterol/LDL-C and LDL-C/HDL-C). The Prosopis cineraria bark extract also significantly (P ≤ 0.001) prevented the atherogenic changes in aorta. Toxicity profile parameters were also examined and remained under normal ranges. Results indicated that Prosopis cineraria bark has hypolipidemic and antiatherosclerotic efficacy along with non-toxic nature.
Treatment of streptozocin induced diabetic wistar rats with the extract caused a significant (P<0.05) reduction in the blood glucose level and significant reduction (P<0.05) in the serum levels of the total cholesterol, Triglycerides and a significant increase (P<0.05) in HDL level. The dose of 750mg/kg showed maximum significant decrease (p<0.05) as compared to other two doses. This result suggests that the hydroalcoholic leaf extract of Prosopis cineraria possess antidiabetic effect on streptozocin induced diabetic Wistar rats.
Pterocarpus santalinoides
The Triglyceride and glucose lowering potential of the leaf extracts of Pterocarpus santalinoides was investigated in dexamethasone induced hyperlipidemia and insulin resistance in rats. Acute toxicity test was performed according to standard methods. An oral glucose tolerance test was carried out in the presence of the extracts in normal rats. Then, graded doses of aqueous and methanol extracts of P. santalinoides (AEPS and MEPS) were administered orally to rats in four groups, respectively, after a 12 h fast followed by subcutaneous administration of dexamethasone (10 mg/kg body wt). Rats in a fifth group received saline (5 ml/kg p.o) followed by dexamethasone (10 mg/kg body wt s.c) and served as positive control while a sixth group served as normal control. The period of extract and dexamethasone administration was 10 days.
Pu’er tea
The anti-obesity and anti-hyperlipidemic effects have been well documented by numerous studies in which Pu-erh tea consumption reduced body weight, weight of adipose pads, serum and hepatic levels of total cholesterol (TC), total Triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) in rats, mice, and human subjects2. However, most of these studies were observational in nature and the underlying mechanisms for these effects have not been determined.
Pueraria lobata (Willd.) Ohwi root extract
Context
Atherosclerosis (AS) is the main cause of cardiovascular and cerebrovascular diseases. Pueraria lobata (Willd.) Ohwi (Fabaceae) has a positiveeffect on improving these diseases.
Objective
The P. lobataeffect on the proliferation and inflammation of vascular smooth muscle in AS and the potential mechanism were investigated.
Materials and methods
By feeding ahigh-fatdiet to 8-week-oldapolipoprotein E knockout mice, anAtherosclerosis model was created. H&E and IHC staining were used to analyse the histopathology of mice. CCK-8, TUNEL, and scratch tests were used to detect cell proliferation, apoptosis, and migration after 24 h treatment, respectively. ELISA was performed to evaluate the level of IL-6 and IL-8. The target miRNA and its downstream target gene were screened by the bioinformatics method; RT-qPCR has conducted to analyse the expression of these genes.
Results
In the aortic tissue andserum of AS mice, puerarin can lower the expression of α-SMA and the inflammatory proteins IL-6 and IL-8. Puerarin (200 M) decreased hVSMC proliferation, migration, and IL-6 and IL-8 secretion by more than half. TheInhibitory impact of puerarin on hVSMC was decreased by overexpression of miR-29b-3p. IGF1 was miR-29b-3p’s downstream target gene. IGF1 expression increased almost 3-fold in AS mice and hVSMC, but miR-29b-3p mimic inhibited it. Theeffect of miR-29b-3p on hVSMC wasreversed when IGF1 was overexpressed.
Discussion and conclusions
Puerarin inhibits the proliferation and inflammation of vascular smooth muscle in AS through the miR-29b-3p/IGF1 pathway. Puerarin may have a beneficialeffect in the treatment ofAtherosclerosis and offer a novel therapy option.
Conclusion: This study further clarified the mechanism of P. lobata extract in improving NAFLD, which provided a scientific basis for developing new drugs to protect liver injury and laid a solid foundation for developing P. lobata Chinese herbal medicine resources.
Puerarin
Roles and mechanisms of puerarin on cardiovascular disease：A review
Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named “Ge gen” in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression ofAtherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance oflipidmetabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and othereffects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.
Excessive Triglycerides (TGs) accumulation in the liver is an important cause for NAFLD (6, 7). The accumulation of TG in hepatocytes is related to four mechanisms: fatty acid uptake, de novo lipogenesis, fatty acid oxidation, and very low-density lipoprotein (VLDL) assembly and secretion
Seventy-six patients with CHD were randomly divided into two groups, 40 in the puerarin group and 36 in the routine treated group. Puerarin 500 mg was given to the former in addition to routine therapy by adding to 250 ml of normal saline for intravenous dripping once a day with a therapeutic course of 3 weeks. The changes of fasting blood glucose (FBG), fasting plasma insulin (FINS), plasma total cholesterol (TC), Triglyceride (TG), low and high density lipoprotein cholesterol (LDL-C & HDL-C) and plasminogen activator inhibitor-1 (PAI-1) activity were measured before and after treatment, and the insulin sensitivity index (ISI) calculated.
Effects of puerarin on rats with type 2 diabetes mellitus
The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured.
The anti-atherosclerotic effects of puerarin on induced-atherosclerosis in rabbits
An atherosclerosis (AS) model was established by feeding 60 rabbits with a high-fat diet and then randomly dividing them into six groups: (1) normal control, (2) model group, (3) simvastatin group, and groups (4), (5), and (6), which received three different dosages of puerarin. Before and after the 90-day treatment period, the fasting serum of all animals was collected to determine the levels of total cholesterol (TC), Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, the aortas were examined for pathomorphological changes. Levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor A (PDGF-A) proteins were assessed using Western blot analysis.
Quercetin
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
Background
Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to reduce hyperlipidaemia and atherosclerotic lesion formation.reversecholesteroltransport (RCT) plays a crucial role in exportingcholesterol from peripheral cells, which is one mechanism utilized in the prevention and treatment ofAtherosclerosis. The aim of this study is to investigate whether quercetin reduceslipid accumulation by improving RCT in vivo.
Methods
apolipoprotein E-deficient mice fed ahigh-fatdiet were used to investigate theeffect of quercetin on RCT by an isotope tracing method, and the underlying mechanisms were clarified by molecular techniques.
Results
These novel results demonstrated that quercetin significantlyimproved [3H]-cholesterol transfer from [3H]-cholesterol-loaded macrophages to the plasma (approximately 34% increase), liver (30% increase), and bile (50% increase) and finally to the feces (approximately 40% increase) for excretion inapolipoprotein E-deficient mice fed ahigh-fatdiet. Furthermore, quercetin markedly increased thecholesterol accepting ability of plasma andhigh-density lipoprotein (HDL) and dramatically decreased the content of malondialdehyde in plasma andoxidized phosphocholine carried by HDL. Therefore, the underlying mechanisms of quercetin in improving RCT may be partially due to the elevatedcholesterol accepting ability of HDL, the increased expression levels of proteins related to RCT, such as ATP-binding cassettes (ABC) A1 and G1, and theimproved antioxidant activity of HDL.
Conclusion
Quercetin accelerates RCT in anAtherosclerosis model, which is helpful in clarifying thelipid-loweringeffect of quercetin.
A ruthenium derivative of quercetin with enhancedcholesterol-lowering activity
A ruthenium(II) p-cymene derivative of quercetin was synthesized and functionally tested forcholesterol-lowering ability via direct 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) inhibition. Ruthenium complexation dramatically increased the inhibition potency of the parent quercetin toward HMGR, with a consequent enhancement of thecholesterol-loweringeffect in hepatic cells.
Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma Triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1% w/w) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%, p < 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver Apob expression (−13%, p < 0.05), which suggests decreased very-low density lipoprotein-TG production.
Quercetin (Q) has rapid metabolism, which may make it worthwhile to focus on the potential activity of its metabolites. Our aim was to evaluate the Triglyceride-lowering effects of Q metabolites in mature and pre-adipocytes, and to compare them to those induced by Q. 3T3-L1 mature and pre-adipocytes were treated with 0.1, 1 and 10 µM of Q, tamarixetin (TAM), isorhamnetin (ISO), quercetin-3-O-glucuronide (3G), quercetin-3-O-sulfate (3S), as well as with 3S and quercetin-4-O-sulfate (4S) mixture (3S+4S). Triglyceride (TG) content in both cell types, as well as free fatty acid (FFA) and glycerol in the incubation medium of mature adipocytes were measured spectrophotometrically. Gene expression was assessed by RT-PCR.
This study was conducted to investigate the effect of quercetin on the Triglyceride (TG) content through the peroxisome proliferator-activated receptor α (PPARα) signalling pathway in broiler hepatocytes. The trial included the following five groups: control, DMSO control, 5 mg/L quercetin, 10 mg/L quercetin and 20 mg/L quercetin. Compared with the control group, the PPARα protein content was significantly increased at 24 h in the groups that received quercetin at 5, 10 and 20 mg/L (p < 0.05), whereas the PPARα mRNA expression was significantly increased at 24, 48 and 72 h (p < 0.05). Compared with the control, the content of the long-chain acyl-CoA synthetase (ACSL), apolipoprotein A1 (ApoA1), liver fatty acid–binding protein (FABP) and TG in the 5-, 10- and 20-mg/L quercetin group was significantly increased at 24, 48 and 72 h (p < 0.05). Moreover, the L-FABP and ApoA1 mRNA expression levels were significantly increased at 24, 48 and 72 h (p < 0.05). Compared with the control, the ApoC3 protein content in the 5-mg/L quercetin group was significantly decreased at 72 h (p < 0.05).
Results: Of 176 articles reviewed, 9 randomized clinical trials were selected based on the inclusion criteria. The pooled results for the effect of quercetin administration on LDL-cholesterol (SMD: -002; 95% CI: -0.15–0.11), HDL-cholesterol (SMD: -0.06; 95% CI: -0.19–0.07), Triglycerides (SMD: 0.05; 95% CI: -0.08–0.18), and total cholesterol (SMD: 0.04; 95% CI: -0.09–0.17) were not significantly different from the control group results. Quercetin administration at doses of ≥250 mg/day (SMD: -0.58 ; 95% CI: -0.94–-0.22) and total dose ≥14,000 mg (SMD: -0.58 ; 95% CI: -0.94–-0.22) significantly reduced LDL levels; however, HDL-cholesterol, Triglycerides, and total cholesterol levels remained unchanged (p > 0.05).
Insight into Triglyceride-reducing potential of quercetin in blood plasma environment
Quercetin has been shown to adsorb plasma Triglycerides and fatty acids. The effects of quercetin on plasma Triglycerides were characterized using various methods, highlighting that the adsorption and removal of Triglycerides were primarily influenced by the dosage of quercetin. The adsorption data were well-represented by both Freundlich and Langmuir type II isotherms, indicating a good fit. Additionally, molecular docking studies revealed that quercetin has inhibitory effects on the peroxidase enzyme, further elucidating its potential biochemical interactions.
Quercetin Induces Hepatic Lipid Omega-Oxidation and Lowers Serum Lipid Levels in Mice
In serum of quercetin-fed mice, Triglycerides (TG) were decreased with 14% (p<0.001) and total poly unsaturated fatty acids (PUFA) were increased with 13% (p<0.01). Palmitic acid, oleic acid, and linoleic acid were all decreased by 9–15% (p<0.05) in quercetin-fed mice. Both palmitic acid and oleic acid can be oxidized by omega (ω)-oxidation. Gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially ω-oxidation. At the gene level, this was reflected by the up-regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3).
Dulbecco’s modified Eagle’s medium (DMEM) was purchased from GIBCO (BRL Life Technologies, Grand Island, NY). Quercetin was purchased from Sigma (St. Louis, MO, USA). Triacylglycerols (TG) were determined by Infinity Triglycerides reagent (Thermo Electron Corporation, Rockford, IL, USA) and protein concentrations of cell extracts were measured with BCA reagent (Thermo Scientific, Rockford, IL, USA). Commercial kits for analyzing free fatty acids and free glycerol were supplied by Roche and Sigma, respectively (Free Fatty Acids, Half Micro Test, Roche, Basilea, Sweden, and F6428, Sigma, St. Louis, MO, USA).
Quillaja saponaria extract
Quillaja saponin extracts are known to reduce plasmacholesterol levels in humans. Here we study the mechanism of thiseffect with Quillaja Dry saponin extract (QD). In vitro model of Triglyceride lipolysis is used to quantify theeffect of QD on the solubilization ofcholesterol and of the lipolysis products (fatty acids and monoglycerides) in thedietary mixed micelles (DMM). We found that QD extract decreases significantly both thecholesterol (from 80% to 20%) and saturated fatty acids (SFA, from 70% to 10%) solubilised in DMM. Series of dedicated experiments prove that QD may act by two mechanisms: (1) direct precipitation ofcholesterol and (2) displacement ofcholesterol from the DMM. Both mechanisms lead to increasedcholesterol precipitation and, thus, rendercholesterol bio-inaccessible. We prove also that the saponin molecules are not the active component of QD, becausehighly purified Quillaja extract with very similar saponin composition does not exhibitcholesterol-lowering or SFA-loweringeffect. Theeffect of QD extract oncholesterol solubilisation is most probably caused by thehigh-molecular weight polyphenol molecules, present in this extract. The reduced SFA solubilisation is caused by Ca2+ ions of relativelyhigh concentration (1.25 wt%), also present in QD extract, which precipitate the fatty acids into calcium soaps.
Quinine (Cinchona bark)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Quinoa oligopeptide
Quinoa diet could significantly reduce the level of blood glucose, Triglyceride, cholesterol, low-density lipoprotein, improve glucose tolerance, as well as improve histological changes of liver tissues in obese mice (P < 0.05 or < 0.01). Besides, quinoa could improve oxidative stress indicators such as GSH, and MDA (P < 0.05 or < 0.01). Furthermore, quinoa can down-regulate mRNA expression of ER stress markers eIF2α, GRP78, and CHOP in the liver of obese mice (P < 0.05 or < 0.01).
Radix Paeoniae Rubra extract
Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensiveeffect or not is seldom studied. This study was to evaluate the protectiveeffect of RPA on hypertensive rats. Alcohol in conjunction with ahigh fatdiet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolicblood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, theblood pressure was significantly increased and thelipid profiles inserum including Triglyceride , totalcholesterol,LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) inserum. The RPA extract significantlyreversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to itseffect on regulatingserum nitric oxide (NO) and endothelin (ET) levels.
In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including Triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels.
Radix polygoni mulitiflori extract
In Vivo Lipid Regulation Mechanism of Polygoni Multiflori Radix in High-Fat Diet Fed Rats
Fatty liver disease (FLD), a kind of lipid metabolic disorder of liver, is a reversible condition in which large vacuoles of Triglyceride fat accumulate in liver cells via the process of steatosis (abnormal retention of lipids within a cell). According to the different inducements of fatty liver, FLD is divided into alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). NAFLD is increasingly recognized as the hepatic manifestation of insulin resistance and the systemic complex known as metabolic syndrome [1, 2]. NAFLD is the most common form of chronic liver disease in adults in the United States, Australia, Asia, and Europe [3–5]. NAFLD is also gaining recognition as a significant early sign of liver cirrhosis and liver cancer [6]; prevalence estimates of NAFLD have used a variety of laboratory and imaging assessments.
Radix Salviae Miltiorrhizae extract
Danshen was able to reduce the risk of the patients with coronary heart disease (CHD), but the mechanism is still widely unknown. Biochemical indices (lipid profile, markers of renal and liver function, and homocysteine (Hcy)) are closely associated with CHD risk. We aimed to investigate whether the medicine reduces CHD risk by improving these biochemical indices. The patients received 10 Danshen pills (27 mg/pill) in Dashen group, while the control patients received placebo pills, three times daily. The duration of follow-up was three months. Theserum biochemical indices were measured, includinglipid profiles (LDLcholesterol (LDL-C), HDL-C, totalcholesterol (TC), Triglycerides (TG),apolipoprotein (Apo) A, ApoB, ApoE, and lipoprotein (a) (Lp(a))); markers of liver function (gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), indirect bilirubin (IBil), and direct bilirubin (DBil)); marker of renal function (uric acid (UA)) and Hcy. After three-month follow-up, Danshen treatment reduced the levels of TG, TC,LDL-C, Lp(a), GGT, DBil, UA, and Hcy (P < 0.05). In contrast, the treatment increased the levels of HDL-C, ApoA, ApoB, ApoE, TBil, and IBil (P < 0.05). Conclusion. Danshen can reduce the CHD risk by improving the biochemical indices of CHD patients.
Mouse peritoneal macrophages were incubated in DMEM with pox-LDL and Rradix Salviae Miltiorrhizae (RSM) to investigate theeffects of RSM on the internalization of peroxidized low density lipoprotein (pox-LDL) by usinglipid analysis and electron microscopy.lipid peroxide (LPO) concentrations were increased slightly in the medium after incubation of macrophages with normalLDL (n-LDL), while decreased significantly in the media after incubation of macrophages with pox-LDL. In the three groups with pox-LDL, it could be found that there was a dose-dependent decrease of concentrations of LPO and totalcholesterol (TCH) in the two RSM groups, and the decrease in the two RSM groups was much greater than in the group without RSM. RSM accelerated a more decrease of LPO thancholesterol contents in the media containing pox-LDL. The ultrastructural studies also showed that RSM induced the accumulation oflipid droplets in the cytoplasm of mouse peritoneal macrophages. The results suggested that RSM could accelerate the phagocytosis and degradation of pox-LDL by macrophages.
Sal treatment markedly reduced weight, body fat index, serum Triglycerides (TG), total cholesterol (TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein (HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as cAMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita.
The concentrations of plasma total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol) and Triglycerides in rats treated with PSME at 150 mg kg day−1 were significantly decreased (P < 0.01), accompanied with significantly decreased concentrations of liver total cholesterol and Triglycerides (P < 0.01). In both drug-treated rats, the concentration of high-density lipoprotein cholesterol (HDL-cholesterol) was significantly elevated (P < 0.01). Intriguingly, short heterodimer partner (SHP) mRNA level was significantly higher in PSME-treated rats (P < 0.01), accompanied with the significantly decreased mRNA level of sterol regulatory element binding protein 1c (SREBP1c) (P < 0.01), which contributed to the decreases of liver and plasma Triglycerides through a farnesoid X receptor-SHP-SREBP1c pathway. ATP-binding Cassette Transporter B11 (ABCB11) and murine Mdr2 P-glycoprotein (also known as ABCB4) were significantly induced by PSME, which were responsible for biliary cholesterol solubility by proper biliary secretion of bile salts and phospholipids. The transactivation assays were used to identify PSME as a farnesoid X receptor/liver X receptor α coagonist.
Radix Scutellariae
Traditional herbal formulas made from Scutellariae Radix (SR), the root of Scutellaria baicalensis, have previously been used in the treatment of inflammatory diseases, such asAtherosclerosis. The aim of the present study was to investigate theeffects of SR on low-density lipoprotein (LDL) oxidation and inflammation in macrophages, which are early events in the development ofAtherosclerosis.high-performance liquid chromatography photo-diode array analysis was used to obtain a three-dimensional chromatogram of SR. The antioxidativeeffects of SR were evaluated by determining its scavenging activities against ABTS and DPPH radicals. TheInhibitoryeffect of SR onLDL oxidation was examined using a thiobarbituric acid-reactive substance assay and a relative electrophoretic mobility assay. In addition, the anti-inflammatoryeffects of SR were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 murine macrophage cells. The results showed that SR exhibited radical-scavenging activities in a dose-dependent manner; in addition, SR attenuated the Cu2+-induced oxidation ofLDL as well as significantly inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW264.7 cells. Furthermore, SR induced the protein expression of heme oxygenase-1 (HO-1) in RAW264.7 cells. In conclusion, the results of the present study demonstrated that SR decreased the oxidation ofLDL and suppressed inflammatory responses in macrophages, which occurred at least in part via the induction of HO‑1. These results therefore suggested that SR may be a potential therapeutic agent for the treatment ofAtherosclerosis.
Also, the liver and visceral fat weights were increased and the lipid profiles in serum and liver homogenate including Triglyceride, total cholesterol, LDL-cholesterol were significantly deteriorated. The SR supplements significantly reversed these altered parameters to near the values of the CD mice. Specifically, the expression of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase in liver homogenate was significantly lowered in the HFDESR group compared with that of either the HFD or HFDE groups, which revealed that the SR extract could afford protection in the alleviation of high fat and alcoholic liver damage.
The effects of Scutellariae Radix (“Ogon”in Japanese) and its flavone components on lipid metabolism in the rat were investigated. Wogonin inhibited deposition of liver Triglyceride and increased serum HDL-cholesterol level in rats fed on corn oil-cholestcrolsodium cholate mixture. Skullcapflavone II reduced the serum total cholesterol level and liver Triglyceride content, and increased serum HDL-cholesterol. Baicalein and baicalin reduced the serum free fatty acid and Triglyceride levels and liver Triglyceride content.
The concentrations of free fatty acid, Triglyceride, total cholesterol, and low density lipoprotein-cholesterol in plasma decreased in SRE-treated groups, although the difference was not significant between control and SRE-treated groups, while that of high density lipoprotein- cholesterol significantly increased in SRE group. The concentrations of total cholesterol and Triglyceride in the liver were tended to decrease in SRE-treated group.
Red clover extract isoflavone
Ten eligible studies (twelve comparisons) with 910 peri- and postmenopausal women were selected for systematic review. The meta-analysis showed changes in serum levels: total cholesterol, −0.29 (95 % CI: −0.53 to −0.06) mmol/L [–11.21 (95 % CI: –20.49 to –13.92) mg/dL], p = 0.0136; LDL-cholesterol, −0.13 (95 % CI: −0.35 to 0.09) mmol/L [–5.02 (95 % CI: –13.53 to 3.48) mg/dL], p = 0.2418; Triglycerides, −0.15 (95 % CI: −0.32 to 0.01) mmol/L [–13.28 (95 % CI: –28.34 to 0.88) mg/dL], p = 0.0592; and HDL-cholesterol, 0.14 (95 % CI: −0.08 to 0.36) mmol/L [5.41 (95 % CI: –3.09–13.92) mg/dL], p = 0.2103. TheI2 statistic ranged from 87.95%–98.30 %, indicating significant heterogeneity.
Red Yeast Rice Extract Monacolin K
Red Yeast Rice for Hypercholesterolemia
Several meta-analyses of randomized controlled clinical trials (RCTs) have verified the lipid-lowering effects of RYR. The most recent, by Gerard et al., included 20 studies with RYR doses varying between 1,200 mg and 4,800 mg/day and containing from 4.8 mg to 24 mg of monacolin K. The meta-analysis demonstrated that RYR reduced LDL-C by an average of 1.02 mmol/L (39.4 mg/dL) after 2 to 24 months of treatment compared to placebo. This effect on LDL lowering was not different from moderate-intensity statins (0.03 mmol/L) such as pravastatin 40 mg and lovastatin 20 mg. The authors also found a small increase in HDL-C (0.07 mmol/L) and a decrease in Triglycerides (TG) of 0.26 mmol/L compared to placebo.14
Resveratrol
effect of red wine consumption on lipoprotein (a) and other risk factors forAtherosclerosis
Epidemiological studies have pointed to the role of alcohol, and red wine in particular, inreducing the incidence of coronary heart disease. This study attempted to distinguish, in vivo, theeffects of com- ponents specific to red wine and those of alcohol on lipoproteins, antioxidant status and membrane fluidity. Volunteers ( n = 2 0 ) were given 200 ml of red wine per day for 10 days. Following a 6-week washout, this was repeated with white wine. Changes within treatment groups were analysed by
paired t tests and repeated measures analysis of variance was used to distinguisheffects of red wine components and alcohol.LDL was prepared by ultracentrifugation and all other assays were by conventional laboratory techniques. Noeffect with either treatment was detected on totalcholesterol, Triglycerides , HDL or measures of antioxidant status, including the susceptibility ofLDL to oxidation. Red wine reducedLDLcholesterol ( p < 0 . 0 1 ) , and both treatments reducedLDL apo B ( p < 0 . 0 1 ) and increasedLDL chohapo B ratio ( p < 0 . 0 1 ) , implying an increase inLDL size. Potential anti-atherogenic changes specific to red wine were reduction in lipoprotein (a) ( p < 0.001) and increased membrane fluidity ( p < 0 . 0 1 ) . These results are not in keeping with the proposed role of red wine components in free-radical protection, but the reduction in lipoprotein (a) merits further investigation.
Naturally Occurring PCSK9 Inhibitors
Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role ofPCSK9 in controlling low-density lipoprotein (LDL)cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficialeffects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurringPCSK9Inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching theirLDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown anInhibitoryeffect onPCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
dietary natural products as emerging lipoprotein(a)-lowering agents
Elevated plasma lipoprotein(a) (Lp(a)) levels are associated with an increased risk of cardiovascular disease (CVD). Hitherto, niacin has been the drug of choice to reduce elevated Lp(a) levels in hyperlipidemic patients but its efficacy inreducing CVD outcomes has been seriously questioned by recent clinical trials. Additional drugs may reduce to some extent plasma Lp(a) levels but the lack of a specific therapeutic indication for Lp(a)‐lowering limits profoundly reduce their use. An attractive therapeutic option is natural products. In several preclinical and clinical studies as well as meta‐analyses, natural products, including l‐carnitine, coenzyme Q 10, and xuezhikang were shown to significantly decrease Lp(a) levels in patients with Lp(a) hyperlipoproteinemia. Other natural products, such as pectin, Ginkgo biloba, flaxseed, red wine, resveratrol and curcuminoids can also reduce elevated Lp(a) concentrations but to a lesser degree. In conclusion, aforementioned natural products may represent promising therapeutic agents for Lp(a)lowering.
Resveratrol protects rabbits against cholesterol diet- induced hyperlipidaemia
The excessive consumption of high cholesterol diet has been associated with an increased incidence of lipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim of these experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet induced hyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control, group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol 400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400.
Studies on resveratrol in a wide range of concentrations on obese mice and adipose cells are necessary to comprehend its range of diverse and contradictory effects. In this study, we examined the anti-obesity effects of resveratrol on high-fat diet (HFD)-induced obese mice at dosages ranging from 1 to 30 mg/kg treatment for 10 wk. We also evaluated the effects of resveratrol on cytotoxicity, proliferation, adipogenic differentiation, and lipolysis of 3T3-L1 cells at concentrations ranging from 0.03 to 100 μM. In HFD obese mice, resveratrol treatment for 10 wk without decreased calories intake significantly attenuated HFD-induced weight gain in a dose-dependent manner. Resveratrol treatment also protected against HFD-induced lipid deposition in adipose tissues and liver.
Inhibition of AMPK by pre-treatment with compound C completely blocked the effects of SY-102. To evaluate their efficacy in vivo, mice were fed a high-fat diet for 5 days, and resveratrol or SY-102 was administered orally for the last 2 days. Oral administration of the SY-102 increased AMPK phosphorylation, followed by reduced hepatic Triglyceride accumulation to a similar extent as resveratrol. These data demonstrate that SY-102, a synthesized derivative of resveratrol, might provide a promising therapeutic effect against fatty liver disease.
Resveratrol: Anti-Obesity Mechanisms of Action
Lipolysis implies the breakdown of triacylglycerols in adipocytes and the release of glycerol and fatty acids. Two major enzymes promote the catabolism of stored triacylglycerols: adipose Triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) [58,59]. ATGL selectively performs the first step in triacylglycerol hydrolysis yielding free fatty acids and diacylglycerols which, in turn, are substrates for HSL [59].
Rhein
Rheum palmatum has been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components of Rheum palmatum that play the antiobesity role are still uncertain. Here, we tested the weight-reducingeffect of two major Rheum palmatum compounds on db/db mouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight in db/db mouse. Usingdiet-induced obese (DIO) C57BL/6 mice, we identified that rhein blockedhigh-fatdiet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and loweredserumcholesterol,LDLcholesterol, and fastingbloodglucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγ antagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy.
We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, and lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver Triglyceride levels, reversed hepatic steatosis, and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and Western blot showed that rhein markedly suppressed the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in the liver.
Since Rheum palmatum is a laxative agent, we determined the Triglyceride and total cholesterol contents in mice feces to assay whether rhein inhibits lipid absorption in the intestine. The results showed that rhein treatment did not increase TG and TC contents in feces (Figure 2(e)), suggesting that the inhibition of obesity by rhein is not caused by inhibition of lipid absorption.
Rhizoma Alismatis
Hypolipidemic effects of Alismatis rhizome on lipid profile in mice fed high-fat diet
Alismatis rhizome treatment resulted in an obvious decrease in serum and liver cholesterol, Triglyceride along with elevated serum high-density lipoprotein cholesterol in hyperlipidemic mice. The histopathological results showed that adipose vacuoles in AR treated mice liver were almost identical to those of normal control mice. Serum alanine transaminase, aspartate aminotransferase and the relative liver weight in AR treated mice were decreased significantly. Alismatis rhizome substantially decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr), while the expressions of sterol regulatory element binding factor 2 (Srebf2) and cholesterol 7alpha-hydroxylase (Cyp7a1) were marginally affected.
Rhizoma Atractylodis Macrocephalae extract
The invention discloses a kind of Rhizoma Atractylodis Macrocephalae extract and purposes witheffect forreducingblood fat, the Rhizoma Atractylodis Macrocephalae extract is prepared by the following method to obtain：Method one, take bighead atractylodes rhizome root medicinal material to pulverize and sieve, be put into extractor and first extract, then separate, Rhizoma Atractylodis Macrocephalae extract is obtained after separation；Separating and keeping CO in extraction process2Flow：55~70L/h；Method two, bighead atractylodes rhizome root medicinal material is taken, crushed, add 3~8 times of amount petroleum ethers, 0.5~3 h of ultrasound, refluxing extraction 1~4 time, every time 0.5~8.0 h；Merging filtrate is concentrated under reduced pressure into organic solvent-free residual.The Rhizoma Atractylodis Macrocephalae extract has regulatingbloodlipid action.It can be widely applied to the medicine or health food witheffect forreducingblood fat.
Atractylodis macrocephalae Rhizoma is widely used as a functional food in Asia. It can enhance glucose and lipid metabolism in the obesity patients with adiposity. In this study, therapeutic effects and the underlying molecular mechanisms of its ethanol extract (AMK) were investigated in db/db mice. Oral treatment with AMK at a dose of 100 mg/kg for three weeks significantly decreased the blood glucose, serum triacylglycerol, total cholesterol, HOMA-IR, endotoxin and IL-1β. Besides, AMK increased the abundance of Bacteroides thetaiotaomicron and Methanobrevibacter smithii in gut microbiota and improved the histological abnormalities of liver, adipocytes, pancreas and small intestine in diabetic mice.
Rhizoma Coptidis extract
It is hypothesized that Rhizoma Coptidis (RC) alkaloids exert theirhypolipidemiceffects primarily by targeting the gastrointestinal tract and liver. Thus, this study was conducted to evaluate the antihyperlipidemic mechanisms of RC alkaloids (at a daily dose of 140 mg/kg for 35 days) inhigh-fat andhigh-cholesterol induced hyperlipidemic B6 mice. After treatment,serumlipid parameters were determined, the expression oflipidmetabolism related genes and pathways such as the sterol regulatory element binding proteins (SREBPs) and bile acid signaling in mice were also investigated. Meanwhile, Illumina sequencing was used to investigate the differences in gut microbiota of B6 mice. The results indicated that RC alkaloids reduced the body weight gain andserum totalcholesterol (TC), Triglyceride (TG), low-density lipoproteincholesterol (LDL-C), total bile acids (TBA) and lipopolysaccharide of B6 mice. Liver fat deposition and epididymal adipose cell size were also deceased in therapy group. RC alkaloids feeding significantly promoted the abundance of Sporobacter termitidis, Alcaligenes faecalis, Akkermansia muciniphila in the gut of mice, whereas, the abundance of Escherichia coli, Desulfovibrio C21_c20, Parabacteroides distasonis was suppressed. The observed antihyperlipidemiceffects of RC alkaloids can also be attributed to their action as agonists of FXR and TGR5, activators for SREBP2,LDLR, UCP2 and CYP7A1,Inhibitors of HMGCR, TXNIP, TLR4 and JNK. Therefore, this study expands current knowledge onhypolipidemic mechanisms of RC alkaloids and presents new evidence supporting a key role for RC alkaloids as regulators oflipid homeostasis by modulation gut microbiota and hepaticlipidmetabolism.
Rhizoma Coptidis: A Potential Cardiovascular Protective Agent
Hyperlipidemia or dyslipidemia, which is characterized by increased plasma Triglyceride concentration and lowered HDL cholesterol, is one of the major risk factor contributing to the progression of CVDs such as CHD and peripheral artery disease. Hence, maintenance of total cholesterol (TC) level within the normal range can be an effective strategy to lower the risk of cardiovascular events (Zou et al., 2016).
Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters
This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, Triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the Triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level.
The antihypercholesterolemic effect of jatrorrhizine isolated from Rhizoma Coptidis
Dyslipidemia is a primary risk factor for the progression of cardiovascular diseases (Celermajer et al. 2012), which is related to abnormal levels of lipids, mainly including total cholesterol (TC), Triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) (Li et al. 2005). It is widely acknowledged that controlling TC level can effectively interfere with the progression of atherosclerosis and reduce cardiovascular events (Manickam et al. 2011).
Rhizoma Polygonati extract
Polygonatum odoratum (Mill.) Druce belongs to the genus Polygonatum family of plants. In traditional Chinese medicine, the root of Polygonatum odoratum, Rhizoma Polygonati Odorati, is used both for food and medicine to prevent and treat metabolic disorders such as hyperlipidemia, hyperglycemia, obesity and cardiovascular disease. However, there is no solid experimental evidence to support these applications, and the underlying mechanism is also needed to be elucidated. Here, we examined theeffect of the extract of Rhizoma Polygonati Odorati (ER) on metabolic disorders indiet-induced C57BL/6 obese mice. In the preventive experiment, the ER blocked body weight gain, and loweredserum totalcholesterol (TC), Triglyceride (TG) and fastingbloodglucose,improvedglucose tolerance test (GTT) and insulin tolerance test (ITT), reduced the levels ofserum insulin and leptin, and increasedserum adiponectin levels in mice fed with ahigh-fatdiet significantly. In the therapeutic study, we induced obesity in the mice and treated the obese mice with ER for two weeks. We found that ER treatments reducedserum Triglyceride and fastingbloodglucose, andimprovedglucose tolerance in the mice. Gene expression analysis showed that ER increased the mRNA levels of peroxisome proliferator-activated receptors (PPAR) γ and α and their downstream target genes in mice livers, adipose tissues and HepG2 cells. Our data suggest that ERameliorates metabolic disorders and enhances the mRNA expression of PPARs in obese C57BL/6 mice induced byhigh-fatdiet.
Although the increasing studies have corroborated the biological activities and great market utilization value of polysaccharide fractions derived from Polygonati rhizome, a well-known edible and medicinal plant, Polygonati rhizome polysaccharides (PRPs) still lack sufficient attention. Herein, we make attempt to systematically summarize recent advances in the extraction, purification, structural characteristics, biological activities, and commercial products of PRPs. Based on the detailed extraction and structural characteristics, the biological activities of PRPs including immune-regulation, anti-osteoporosis, anti-Alzheimer’s disease, anti-diabetes and anti-atherosclerotic, are emphatically summarized, as well as the possible related mechanisms. Most importantly, about 365 kinds of commercial functional foods and over 500 patents related to PRPs as the main raw material were analyzed to explore the status quo and bottleneck for the development and utilization of PRPs.
Rhizoma Polygonati falcatum (RPF) has been used as a traditional herbal medicine in Asia, because of its anti-hyperglycemic, anti-triglycemic, and anti-tumor activity. In this study, we determined the anti-adipogenic potential of RPF extract and its component kaempferol in 3T3-L1 adipocytes, and the underlying molecular mechanism(s) using microarray analysis. Adipocyte differentiation of 3T3-L1 cells was significantly impaired by RPF extract and kaempferol as monitored by Oil Red O staining and quantitative measurement of lipid accumulation.
Roselle (Hibiscus sabdariffa)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Effects of Hibiscus sabdariffa Extract Orally Administered on Lipid Parameter of Albino Rats
Lipid parameters were investigated in albino rats of different groups after administration of 0.0mg/ml, 25.0mg/ml, 50.0mg/ml, 100.0mg/ml and 200.0mg/ml of aqueous extract of Hibiscus sabdariffa. The results obtained show that total cholesterol, Triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels of the control group were 112.70±1.84, 103.80±1.22, 26.14±1.71 and 66.35±1.02 respectively. The control results when compared to the study groups of B, C, D and E whose values were 89. respectively showed a significant decrease (p≤ 0.05) for cholesterol, Triglyceride and LDL-cholesterol. However, HDL-cholesterol showed a significant increase (P≤ 0.05) when compared with the control group. These findings implies that the administration of Hibiscus sabdariffaaqueous extract have protective effects against hyperlipidemia related disorders such as cardiovascular diseases.
Rosa laevigata Michx
The protective effects of total saponins from Rosa laevigata Michx fruit (RLTS) in high-fat diet (HFD)-induced rats were investigated. The results showed that oral administration of RLTS attenuated hepatic steatosis, significantly reduced the levels of body weight, alanine transaminase, aspartate transaminase, total cholesterol, total Triglyceride, free fatty acids, low density lipoprotein, blood glucose, insulin and malondialdehyde, and increased high density lipoprotein and glutathione levels compared with the model group. Further investigations showed that RLTS affected fatty acid synthesis, fatty acid β-oxidation, fatty acid ω-oxidation, total cholesterol and Triglyceride metabolism and synthesis. Moreover, the extract obviously suppressed HFD-induced oxidative stress and inflammation. These results suggest that RLTS should be developed to be one functional food or health product against non-alcoholic fatty liver disease (NAFLD) in the future.
Rose extract
Objective: HyperTriglyceridemia or elevated serum Triglyceride (TG) is a leading risk factor for developing atherosclerotic cardiovascular diseases. This clinical study was designed to test the potential of polyphenol-rich extract from Rosa rugosa petals (PE) for improving hyperTriglyceridemia and other types of dyslipidemia. Methods: An open-label clinical study was conducted on 19 male and female adult subjects with elevated serum TG (120-399 mg/dL), who were intervened the study diet containing (in a daily dose) 200 mg of PE once daily for sss4 weeks. The serum levels of TG and cholesterols were measured at baseline and week-4. The efficacy was evaluated by comparing the measurements at these two timepoints. Results: A significant decrease (P < 0.05) in serum TG, as well as in serum total cholesterol and non HDL-cholesterol, and a marginally significant decrease (P = 0.070) in serum LDL-cholesterol were observed, while serum HDL-cholesterol was virtually not changed. The study diet was well tolerated without any untoward side effect. Conclusions: The PE-containing diet appears to have benefits in improving hyperTriglyceridemia and hypercholesterolemia.
Rosemary (Rosmarinus officinalis)
Investigation of theeffect of oral administration of rosemary (Rosmarinus officinalis) as powder onlipid profiles andbloodglucose in healthy and type-2 diabetic human patients was done. Forty-five type-2 diabetic patients and 15 non-diabetic persons of age 40 years or older participated in the study. Patients selected in this study had fastingbloodglucose in the range 160-300 mg/dl, andhighlipid profiles levels. In addition, patients were allowed to take their routinediet and usual diabetic medicine but not any other health medication. All participants were told to take 3 g of rosemary per day for 4 weeks. Plasmalipid profiles andbloodglucose were measured before and after rosemary administration. Significanteffect of rosemary is obviously noticed in diabetic patients.lipid profiles (low density lipoproteinLDL, Triglycerides andcholesterol) decreased by 31-35%, andbloodglucose decreased by 21%. In addition,high density lipoprotein (HDL) in both diabetic and non diabetic persons increased by 22%. Rosemary showed favorable changes inlipid profiles andbloodglucose levels in type-2 diabetic patients. Key words: Type-2 diabetes, rosemary, dyslipidemia,bloodglucose.
Sixteen flavonoids (1–16) including two new ones, named officinoflavonosides A (1) and B (2) were obtained from the aerial parts of Rosmarinus officinalis. Among the known ones, 6, 10, and 13 were isolated from the rosmarinus genus for the first time. Their structures were elucidated by chemical and spectroscopic methods. Moreover, the effects on sodium oleate-induced Triglyceride accumulation (TG) in HepG2 cells of the above-mentioned compounds and 16 other isolates (17–32) reported previously to have been obtained in the plant were analyzed. Results show that eight kinds of flavonoids (compounds 1, 2, 3, 6–9 and 11) and seven kinds of other known isolates (compounds 17–20, 23, 26 and 31) possessed significant inhibitory effects on intracellular TG content in HepG2 cells. Among them, the activities of compounds 1 and 20 were comparable to that of orlistat, which suggested that these compounds in this plant might be involved in lipid metabolism.
Hypolipidemic effects of Rosmarinus officinalis L
Dyslipidemia is one of the major risk factors for cardiovascular diseases (CVDs). Current strategies are not effective in the management of dyslipidemia. Thus, there is a necessity to find new preventative and therapeutic approaches. In recent years, herbal medicine has drawn great attention regarding the prevention and management of dyslipidemia. Rosmarinus officinalis, commonly known as rosemary, is an evergreen shrub containing several polyphenols.
Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: a review
Metabolic syndrome is defined by a constellation of complex coexisting cardiometabolic risk factors such as hyperglycemia, dyslipidemia, inflammation, abdominal obesity, coagulopathies, and hypertension that raise the risk of diabetes mellitus and cardiovascular disease. Recently, there has been an increasing interest in the use of herbs and natural compounds in prevention and treatment of diseases and a large number of published articles have focused on this issue. Rosmarinus officinalis L. or rosemary (Lamiaceae) is a rich source of phenolic phytochemicals having significant anti-oxidant, anti-inflammatory, hypoglycemic, hypolipidemic, hypotensive, anti-atherosclerotic, anti-thrombotic, hepatoprotective, and hypocholesterolemic effects. The purpose of this review is to highlight the interesting pharmacological effects of rosemary, and its active compounds, and the related mechanisms in the management of metabolic syndrome that are documented in in vitro and in vivo studies.
Rutin
Hyperlipidemia was confirmed by the increase in total cholesterol (TC) and Triglycerides (TG). Hematological alterations, elevated reactive oxygen species (ROS) levels, and increased myeloperoxidase (MPO) and ADA activities were observed in hyperlipidemic rats. Curcumin and the curcumin/rutin association decreased TG and increased high-density lipids (HDL) levels. The pretreatments prevented changes in the hematological parameters, decreased the activities of MPO in plasma and ADA in serum and cells. Cholesterol and ROS levels were not altered by the pretreatments. Our results show that pretreatments with rutin and/or curcumin prevent the hyperlipidemia-induced inflammation. Pretreatments with curcumin and/or rutin are potential complementary therapies in the prevention of hyperTriglyceridemia and inflammation.
Saffower Yellower
hypolipidemic effect of safflower yellow and primary mechanism analysis
We examined thehypolipidemiceffect of safflower yellow (SY) on hyperlipidemic mice and its influence on the biological synthesis ofcholesterol in cells. Over 4 weeks, the levels of totalcholesterol, Triglyceride , low-density lipoproteincholesterol, andhigh-density lipoproteincholesterol inserum were detected using a kit; mouse liver samples were acquired for paraffin sections, and mouse liver cells were observed under light microscope. Chinese hamster ovary cells were cultured in vitro, and an amphotericin B-cell model was adopted to observe theInhibitoryeffect of SY on the biological synthesis of intracellularcholesterol. An enzyme-linked immunosorbent assay was used to detect the survival rate of Chinese hamster ovary cells. The middle andhigh doses of SY significantly reduced the levels of totalcholesterol, Triglycerides , and low-density lipoproteincholesterol in theserum of hyperlipidemic mice and low-density lipoproteincholesterol/high-density lipoproteincholesterol ratio (P < 0.05), and the fatty liver of hyperlipidemic mice was significantly alleviated. SY had a protectiveeffect on Chinese hamster ovary cells following amphotericin B injury (P < 0.01). SY exerts significanthypolipidemiceffects and prevents fatty liver in a mechanism associated with inhibition of the biosynthesis of intracellularcholesterol.
Saffron (Crocus sativus)
Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety
Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverseeffects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order toeffectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
Background and aims
Crocin is the most important compound derived from saffron, with several medicinal properties, including hypolipidemic activity. The aim of this study was to assessment of the effect of crocin on the serum levels of liver enzymes and lipid profile in patients with non-alcoholic fatty liver disease (NAFLD).
Methods
In this double-blind clinical trial, 60 patients with the non-alcoholic fatty liver disease were randomly recruited to consume either 15 mg crocin (n = 30) or placebo capsules (n = 30) once a day for 8 weeks. Aspartate and alanine aminotransferase, Triglycerides and high-density lipoprotein cholesterol (HDL-c) were measured. Low density lipoprotein cholesterol (LDL-c) was determined by Friedewald formula.
Results
Statistical analysis showed that serum levels of Triglyceride (p = 0.0008), aspartate transaminase (AST) (p = 0.03) and alanine transaminase (ALT) (p = 0.0001) were significantly decreased in the crocin group. Moreover, changes in HDL-C and LDL-C levels were not statistically significant in the two groups.
Conclusion
Crocin considerably improved liver functions and Triglycerides levels in NAFLD patients in an 8-week randomized clinical trial. The results deserved further investigations with more accurate methods to confirm.
Background and aims: We aimed to evaluate a possible atheroprotective effect of saffron aqueous extract (SFE), and its potential anti-inflammatory mechanisms, in apoE knockout (ApoE-/-) mice.
Methods: Fifty male, ApoE-/- mice, fed a high-fat diet (HFD) for 12 weeks, were randomized into 5 groups: (1) baseline group, euthanatized, without intervention, (2) three saffron groups, receiving HFD and 30,60,90 mg/kg/day of SFE, respectively, for four weeks, per os through gavage, after reconstitution in water for injection (WFI), (3) control group (COG), receiving daily HFD and the same volume of WFI (four weeks). After blood sampling and euthanasia, aortic roots were excised and analyzed for gene expression and/or percentage of aortic stenosis, relative content of macrophages, smooth muscle cells (SMCs), connective tissue, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinases-2,-3,-9 (MMP-2,-3,-9) and their inhibitor (TIMP-2) and IL-6. SFE doses were determined by a pilot serum pharmacokinetic study in C57BL/6J wild-type mice.
Results: SFE did not affect body weight and total cholesterol levels (p > 0.05), while high SFE dose significantly ameliorated glucose and Triglycerides profiles compared to other groups (p < 0.05). SFE considerably decreased aortic stenosis in a dose-dependent manner (p < 0.05). Furthermore, increasing SFE doses proportionally reduced macrophages content and increased within plaques content of collagen, elastin, and SMCs, promoting more stable plaque phenotype compared to COG (p < 0.05). Those effects seemed to be associated with a considerable reduction (>30%) in IL-6, TNF-α, MCP-1, MMP-2,-3,-9 (p < 0.05) and MMP-2/TIMP-2 ratio.
Conclusions: SFE exerted dose-dependent anti-atherosclerotic and plaque-stabilizing effects in Apo-E-/- mice, probably mediated by a favorable modification of inflammatory mechanisms, which requires further investigation.
Background/aims: A growing body of evidence supports an important role of inflammatory cytokines in the development and progression of the Metabolic Syndrome (MetS), which explains, at least in part, its relationship with an increased cardiovascular-risk. Several studies have reported the therapeutic-impact of crocus-sativus in a preclinical/clinical setting. Here we have explored the effects of crocus-sativus, on the serum concentrations of twelve serum cytokines in subjects with MetS in a randomized control trial.
Methods: Forty four adult volunteers, who met the diagnostic-criteria of MetS, were enrolled and randomly divided into 2 groups, to receive 100 mg/day crocus-sativus for 12 weeks. 12 cytokines, including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, and VEGF were measured using sandwich chemi-luminescence assays before/after therapy.
Results: Individuals with MetS who received crocus-sativus had significantly (P<0.05) lower levels of total-cholesterol, low density-lipoprotein-cholesterol and Triglyceride (TG), fasting-blood-sugar and hsCRP, however the serum concentration of high density-lipoprotein-cholesterol markedly enhanced after therapy (e.g., TG level reduced from 148.86±71.49 to 101.90±38.19 after therapy, P= 0.003). Moreover, we observed that treatment with Crocus-sativus affected the serumconcentrations of some pro-/anti-inflamatory cytokines. In particular, the level of VEGF was increased from 12.64 pg/mL (95% CI: 9.60-17.67) to 16.59 (95% CI: 11.33-35.98, P= 0.033. Similar results were detected for IL-6 and EGF.
Conclusion: Our findings provide a novel insight into the therapeutic effects of this therapy in MetS patients via perturbation of serum cytokines and reducing the levels of Triglyceride and LDL/TC, but further studies are required in larger populations.
The aim of the present study was to evaluate the hypolipidemic and antioxidant potential of saffron and its active constituent, crocin, in hyperlipidemic rats. The animals fed either with normal fat diet or high fat diet were administered orally saffron (25, 50, and 100 mg/kg) or crocin (4.84, 9.69, and 19.38 mg/kg) in their respective groups for five consecutive days. Biochemical estimations of Triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione peroxidase enzyme activity (GSHPx), total glutathione (GSH), and oxidized glutathione (GSSG) in serum and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive species (TBARS), ferric reducing/antioxidant power (FRAP), and total sulfhydryl (SH) groups in liver tissue homogenate were carried out.
Saikosaponins isolated from Bupleurum falcatum L. II.
Several metabolic actions of saikosaponins isolated from the root of Bupleurum falcatum L. were examined using albino rats. Hepatic protein synthesis from leucine-14C(U) was enhanced. Glycogen content in the liver was increased, but oxidation ofglucose-14C(U) in the liver was not changed. Elevation of plasma levels ofcholesterol, Triglycerides and p-ospholipids bycholesterol feeding was reduced. Although hepatic lipogenesis and cholesterogenesis from acetate-1-14C ofglucose-14C(U) were stimulated, the elimination of i.p. injectedcholesterol-4-14C from plasma was acclerated. Fecal excretion of i.p. injectedcholesterol-4-14C, expressed as total-14C including bile acids-14C and neutral sterols-14C, was increased. Among the saikosaponins isolated from Bupleurum falcatum L., saikosaponins a and d, but not c, had metabolic actions as well as anti-inflammatory action. These metabolic actions and anti-inflammatory action of saikosaponins may confirm the clinical application of Bupleurum falcatum L, which has been widely used in the prescriptions of the oriental medicine, and may suggest possible mechanisms for the actions of its active principles.
The heterodimer then interacts with PPAR response elements (PPREs) to regulate the expression of core genes such as acyl-CoA oxidase 1 (Acox1) and carnitine palmitoyltransferase 1α (Cpt1α) (Yu et al., 2015). PPARα agonists such as fibrates decrease plasma Triglycerides (TG) levels and serve as therapeutic agents for dyslipidemia (Bougarne et al., 2018). In contrast, PPARα deficiency in mice has been shown to increase the susceptibility to hepatic steatosis and MAFLD (Ip et al., 2003). The above evidence indicates that drugs targeting SREBP1c and PPARα are worthy of being developed in clinical preparation for the management of MAFLD.
Salix alba L. tree
Background: Low density lipoprotein oxidation is a major pathogenic pathway inAtherosclerosis. Previous studies suggested that aspirin, a commonly prescribed drug in patients withAtherosclerosis, when given in a dose of 300 mg/day may decreaseLDL susceptibility to oxidative modification. However, theeffect of the more common lower dose aspirin onLDL oxidation is not known.
Objectives: To examine theeffect of aspirin administration (low dosage) on the susceptibility ofLDL to oxidative modification in healthy volunteers.
Methods: Aspirin 75 mg was administered daily for 2 weeks to 10 healthy volunteers selected from the medical staff and students at the faculty of medicine. The main outcome measure was ex vivo oxidation ofLDL by ultraviolet C irradiation or by peroxyl free radicals generated by AAPH (2,2′-azobis 2-amidinopropane hydrochloride). The extent ofLDL oxidation was determined by measuring the formed amounts of thiobarbituric acid-reactive substances,lipid peroxides and conjugated dienes.
Results: Following exposure to UVc irradiation there was a significant (P 0.01) increase (10.8%) in TBARS concentrations and a significant (P < 0.05) increase (5.4%) in PD concentrations inLDL withdrawn after aspirin treatment as compared toLDL withdrawn before aspirin treatment. Following incubation with AAPH there was a significant (P < 0.05) increase (15%) in PD concentrations and a significant (P < 0.05) reduction (10%) of theLDL oxidation lag time inLDL withdrawn after aspirin intake as compared toLDL withdrawn before aspirin treatment.
Conclusions: Aspirin treatment given to healthy volunteers at a dose of 75 mg/day increased the susceptibility of their plasmaLDL to oxidative modification ex vivo. Our study provides, for the first time, in vivo evidence of pro-oxidative properties of aspirin already suggested by previous in vitro trials.
A study was conducted to determine the effects of dietary hydroalcoholic willow bark extract powder (HWE) supplemented to broilers (14-42 days old) that were exposed to heat stress, on the performance, serum biochemical parameters, liver oxidative status and caecal microflora. The feeding trial was conducted on 120 Cobb 500 broilers (14 days old), assigned to three treatments (T0, T25, and T50), each treatment consisting of eight replicates (five chicks per replicate). The broilers were housed in an experimental hall at a 32 °C constant temperature and 23 hours light regimen. Unlike the dietary control treatment (T0), the experimental treatments were supplemented with 25 g HWE powder/100 kg diet (T25), and 50 g HWE powder 100 kg diet (T50), respectively. Dietary HWE powder did not affect the broilers’ performance significantly (14-42 days). A significantly lower amount of malondialdehyde was noticed in the liver of broilers from T25 and T50 treatments in comparison with broilers from T0. Also, the serum cholesterol, Triglycerides and alanine aminotransferase were significantly lower in broilers fed with T50, compared with those fed with T0. At 35 and at 42 days, the broilers from T25 and T50 recorded a significantly lower number of E. coli and staphylococci and a higher number of lactobacilli in the caecum than those of T0. It could be concluded that supplementation of dietary HWE powder reduced some of the adverse effects of heat stress, the most effective being the level of 50 g/100 kg diet.
Sambiloto (Andrographis paniculata)
cholesterol is one of the causes of coronary heart disease. The research objective is Assessing dosege of Sambiloto extract inreducingbloodcholesterol levels rats (Rattus norvegicus) hypercholesterolemia. The research method is experimental, using Completely Randomized Design (CRD) 3 replications, 6 treatments are: 1) D0 = normal control; 2) D1 = positive control ofcholesterol; 3) D2 = comparator simvastatin 2mg/200 g body weight; 4) D3 = dose of 100 mg sambiloto/200 g body weight; 5) D4 = dose 200 mg sambiloto / 200 g body weight; 6) D5 = dose of 400 mg sambiloto/200 g body weight. Rats that have been tested are white male Wistar rats aged 2 months, weight ± 200 g. Analysis using Anova, and further test using DMRT, α 5%. The results of the experiment showed that sambiloto extract of 100 mg/200 g body weight, 200 mg/200 g body weight; 400 mg/200 g body weight and a simvastatin comparator 2 mg/200 g body weight all of that can reduce the totalcholesterol level of ratsblood that be made hypercholesterolemia. Interestingly, the dose of 400 mg/200 g body weight has the same ability as simvastatin dose of 2 mg/200 g body weight inreducing totalbloodcholesterol levels of rats by 51%, considering the risk of hypocholesterolemia.
HyperTriglyceridemia is one of the risk factors for cardiovascular disease, and reduction of Triglyceride (TG) level is recommended in clinical practice guidelines for the treatment. Recently, andrographolide, a main active compound of Andrographis paniculata has been shown to possess hypolipidemic effects in animals. Objective: To investigate the TG-lowering effects of A. paniculata extract (APE) in patients with hyperTriglyceridemia (TG >150 mg/dL) using gemfibrozil treatment as the reference.
Treatment with andrographolide and extract showed an increase in glucokinase (GK; P < 0.05), hexokinase (HK; P < 0.05), and lactate dehydrogenase (LDH; P < 0.05) enzyme levels respectively. Significant reductions were observed in serum cholesterol (P < 0.05), Triglycerides (P < 0.05), free fatty acids (P < 0.05), and liver glucose 6-phosphatase (G6P’Tase; P < 0.05) enzyme levels on treatment with andrographolide and extract. Glucose 6-phosphate dehydrogenase (G6PDH; P < 0.05) level also showed a significant increase on treatment with andrographolide and extract. Liver antioxidant status (P < 0.05) also improved significantly on treatment with andrographolide and extract.
The ethanolic extract of A. paniculata at a dose of 400 mg/kg body weight twice daily for 2 weeks to diabetic rats was shown to produce a 49.8% reduction in fasting serum Triglyceride levels. This was reported to be greater than the 27.7% decline that was achieved with 500 mg/kg body weight twice daily for 14 days [24]. An aqueous extract (50 mg/kg body weight) administered to streptozotocin-diabetic rats resulted in a 52.9% reduction in blood glucose levels.
Salvianic acid B
The results showed that SalB significantly reduced the body weights and liver weights, and ameliorated plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), Triglyceride (TG), hepatic free fatty acid (FFA), total cholesterol (TC) levels, and hepatic TG and TC levels in ob/ob mice. SalB reduced the number of lipid droplets and inhibited hepatic lipogenesis by regulating peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), stearoyl-Co A desaturase 1 (SCD1), and cluster of differentiation 36 (CD36). Compared to ob/ob mice, the lower expressions of the pro-inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and F4/80, were observed after SalB treatment. Importantly, SalB treatment inhibited the activation of NLRP3 inflammasome and reduced the severity of liver inflammation. Our findings suggested that SalB improved NAFLD pathology in ob/ob mice by reducing hepatic lipid accumulation and NLRP3 inflammasome activation, which might be the potential hepatoprotective mechanism of SalB.
Salvianolic acid A
The blood glucose, body weight, and food intake of rats were examined. After 7 and 8 weeks of continuous administration, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed, respectively. Serum fasting insulin (FINS), total cholesterol (TC), Triglyceride (TG), and free fatty acid (FFA) were determined. Liver tissues were stained using hematoxylin–eosin (HE) and oil red O staining. Fecal samples were analyzed by 16S rRNA gene sequencing. Small intestinal tissues were stained using HE and immunohistochemistry. The tight junction proteins (ZO-1/Occludin/Claudin-1) and serum levels of LPS/TNF-α/IL-6 were evaluated. SalA reduced insulin resistance, liver injury, serum FFA, liver TC and TG levels in ZDF rats, and improved lipid metabolism.
Seabuckthorn
cholesterol lowering POTENTIAL OF SEABUCKTHORN
The present study was designed to investigate theeffect of Seabuckthorn onlipid profile, its antioxidant potency and itseffect on hemodynamic changes and baroreceptor mediatedblood pressure regulatory mechanisms in hypercholesterolemic rats. For induction of hypercholesterolemia rats were fed with fructose in drinking water and in vivo experiment had done to investigate the hemodynamic as well as the biochemical profile of seabuckthorn. It is a natural product and investigations carried out so far do not report any apparent toxiceffect. Based on the results of the present study, it is recommended that seabuckthorn pulp oil may be supplemented with normaldiet for providing protection against hypercholesterolemia. The fall inblood pressure of animals having a normallipid profile suggests that it may have a hypotensiveeffect. Hence, its use as alipid-lowering agent needs to be carefully monitored especially in people with cardiac problems. Conclusive evidence shows that baroreceptor modulation of heart rate is impaired in animals and patients withAtherosclerosis. It has been suggested that oxygen free radicals produced inAtherosclerosis may contribute to baroreceptor dysfunction. Seabuckthorn prevented the development of hypertension and reduced insulin resistance in chronically fructose-fed rats and reduced vascular superoxide anion production throughlowering the NAD (P) H oxidase activity in hypertensive rats.
Sea buckthorn has been used in clinical trials to treat metabolic syndrome in recent years (Table 6). A study in obese children assessed the effects of sea buckthorn pulp oil treatment (800 mg/d for 60 d) on inflammation, systemic redox status, and endothelial function. The treatment was shown to prevent atherosclerosis (AS) by strongly reducing Triglycerides (TG), cholesterol, and blood pressure, and weakly reducing oxidative stress, inflammation, and insulin resistance [53]. Another human study investigated the effects of dietary supplementation with phenol-rich sea buckthorn powder. An analysis of plasma with nuclear magnetic resonance (NMR) fingerprinting after meals showed that the treatment delays postprandial lipid changes and inhibits increases of 3-hydroxy butanoic acid and N-acetyl glycoproteins compared to untreated controls
Silymarin
effect of silymarin and its polyphenolic fraction on cholesterolabsorption in rats
This study evaluated the influence of silymarin (SM) and polyphenolic fraction (PF) of silymarin oncholesterolabsorption in rats fed onhighcholesteroldiet (HCD). HCD induced a remarkable increase in hepatic, plasma, VLDL andLDLcholesterol, a decrease in HDLcholesterol and an elevation in triacylglycerol (TAG) levels in plasma, VLDL and in the liver. SM and PF were administered asdietary supplements (1.0%) in HCD for 18 days. Intestinalcholesterolabsorption was measured by dual-isotope plasma ratio method, which calculates percent ofcholesterolabsorption from the ratio of two labelledcholesterol doses, one given intragastrically (14C) and one intravenously (3H). Silymarin and PF significantly reducedcholesterolabsorption in rats fed on HCD and caused significant decreases in plasma and VLDLcholesterol and content ofcholesterol and TAG in the liver. The level of HDLcholesterol was significantly increased after silymarin, but not after administration of PF. The levels of TAG in plasma and VLDL were not affected by either silymarin or PF. These results suggest that the inhibition ofcholesterolabsorption caused by silymarin and its polyphenolic fraction could be a mechanism contributing to the positive changes in plasmacholesterol lipoprotein profile and inlipid content in liver.
effect of Silybin onlipid Profile in Hypercholesterolaemic Rats
Introduction
Hyperlipidemia is a major cause ofAtherosclerosis andAtherosclerosis associated conditions, such as Coronary Heart Disease (CHD), ischaemic cerebrovascular disease and peripheral vascular disease. Though there arehypolipidemic drugs available, the search for a more efficacious hypolipidemic agent was always going on.
Aim
To study theeffect of Silybin onlipid profile in Hypercholesterolaemic rats.
Materials and Methods
After grant of permission from animal ethics committee, the animals were divided into four groups of eight each (normal control, Experimental control withhighcholesteroldiet,highcholesteroldiet + Silybin 300mg,highcholesteroldiet + Silybin 600mg). At the end of 60 days the animals in all the groups were subjected to overnight fasting followed by plasma and liver biochemical analyses.
Statistical Analysis
The data were analysed by ANNOVA followed by Duncan’s multi range test and the value of p≤0.05 was used as the criterion for statistical significance.
Results
The rats fed onhighcholesteroldiet showed significant increase inserum totalcholesterol, Triglycerides ,LDL-C and VLDL-C. Treatment with Silybin significantly decreasedserum totalcholesterol (24%), Triglycerides (21%),LDL-C (24%) in a dose dependent manner. Rats treated with Silybin (300 and 600 mg/kg) showed significant increase in hepatic HDL –C and decrease in otherlipid profiles.
Conclusion
Treatment with Silybin significantly decreased bothserum and hepatic totalcholesterol, Triglycerides , VLDL-C,LDL-C and increased HDL-C at both doses.
Hypolipidemic effect of Silymarin in Dyslipidaemia of Different Etiologies
Fifty seven patients with dyslipidaemia of various etiologiesare involved in this clinical trial. They are randomized into three groups treated witheither 400mg / day silymarin (gr. A) or 20 mg / day lovastatin (gr. B) or a combinationof 200 mg/day silymarin and 10 mg/day lovastatin (gr. C) for 2 months, only 45patients complete the study . Serum lipid profile (total cholesterol, Triglycerides, LDL-C, VLDL-C and HDL-C) and liver functions indices (SGOT, SGPT, total bilirubin)were evaluated each month during the follow up period.
Sophora japonica L.flower
effect of Sophora japonica Extract onlipid Content inhigh Fatdiet Fed Rats
Theeffect of hot water extract of Sophora japonica Linne (Koehwa) flower onlipid content were studied in terms of hematological variables in rats fed withhigh fatdiet. Experimental rats were divided into basaldiet only (BDG),high fatdiet control (FDC),high fatdiet and 6% Sophora japonica extract powder (FD6S), andhigh fatdiet and 12% Sophora japonica extract powder (FD12S) groups. The levels of hematological variables were not significantly different among the four groups, whereas transferrin concentration and glutamic oxaloacetate transaminase (GOT) activity inserum metabolic variables were significantly different. Transferrin concentration washigher in the FD6S and FD12S groups than in BDG and FDC groups. FD6S and FD12S groups showed significantly lower level of GOT activity. Totalcholesterol levels of FD6S and FD12S groups were 220.38 and 205.02 mg/dL in theserum, respectively. Totalcholesterol levels of FD6S and FD12S groups were lower than that of FDC group (341.38 mg/dL) and the same level as that of FDG group (216.18 mg/dL). HDL- andLDL-cholesterol levels of FDC group were 26.84 and 62.91 mg/dL, whereas those of FD12S group were 38.02 and 44.16 mg/dL. Supplementation of 12% Koehwa extract powder remarkably increased HDL-cholesterol level and greatly decreasedLDL-cholesterol level. Atherogenic indices in FD6S and FD12S groups were significantly lower than those of yje FDG group. The FD12S group supplemented with Koehwa extract showed lower Triglyceride concentration than that of the FDC group. These results suggested thatdietary supplementation of Koehwa extracts did not have any adversaryeffect on the hematological variables, butimproved thelipid content and reduced hepatic damage of thehigh fat fed rats.
Soy bean extract isoflavone
Background:Clinical trials have reported thecholesterol-lowering effects of soy protein intake, but the components responsible are not known.
Objective:This meta-analysis was primarily conducted to evaluate the preciseeffects of soy isoflavones onlipid profiles. Theeffects of soy protein that contains enriched and depleted isoflavones were also examined.
Design:PUBMED was searched for English-language reports of randomized controlled trials published from 1990 to 2006 that described theeffects of soy protein intake in humans. Eleven studies were selected for the meta-analysis.
Results:Soy isoflavones significantly decreasedserum totalcholesterol by 0.10 mmol/L (3.9 mg/dL or 1.77%; P= 0.02) andLDLcholesterol by 0.13 mmol/L (5.0 mg/dL or 3.58%; P< 0.0001); no significant changes in HDLcholesterol and triacylglycerol were found. Isoflavone-depleted soy protein significantly decreasedLDLcholesterol by 0.10 mmol/L (3.9 mg/dL or 2.77%; P= 0.03). Soy protein that contained enriched isoflavones significantly decreasedLDLcholesterol by 0.18 mmol/L (7.0 mg/dL or 4.98%; P< 0.0001) and significantly increased HDLcholesterol by 0.04 mmol/L (1.6 mg/dL or 3.00%; P= 0.05). The reductions inLDLcholesterol were larger in the hypercholesterolemic subcategory than in the normocholesterolemic subcategory, but no significant linear correlations were observed between reductions and the starting values. No significant linear correlations were found between reductions inLDLcholesterol and soy protein ingestion or isoflavone intakes.
Conclusions:Soy isoflavones significantly reducedserum total andLDLcholesterol but did not change HDLcholesterol and triacylglycerol. Soy protein that contained enriched or depleted isoflavones also significantlyimprovedlipid profiles. Reductions inLDLcholesterol were larger in hypercholesterolemic than in normocholesterolemic subjects.
Soy leaf extract
Soy-leaf extracts exert their cardioprotectiveeffects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate theserumlipid profile. In this study, we investigated the atheroprotectiveeffects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) andhigh-cholesteroldiet (HCD)-fed low-density lipoprotein receptor deficient (LDLR−/−) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Westerndiet-fedLDLR−/− mice by 46% (p < 0.01) compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1), TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9), and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-inducedAtherosclerosiseffectively.
Spergularia purpurea
The purpose of this study was to examine theeffect of single and repeated oral administration of the aqueous extract of Spergularia purpurea (SP) at a dose of 10 mg/kg in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of SP induced a significant decrease of the plasmacholesterol concentrations 6 h after a single oral administration (P<0.05) and 2 weeks after repeated oral administration (P<0.05). The plasma Triglycerides levels increased significantly 6 h after a single oral administration (P<0.05) and decreased 2 weeks after repeated oral administration (P<0.05).
In diabetic rats, SP treatment caused a significant decrease of plasmacholesterol levels after a single (P<0.01) and repeated (P<0.01) oral administration. A significant increase of Triglycerides levels was observed 6 h after a single oral administration of the SP aqueous extract (P<0.01). One week after repeated oral administration of SP aqueous extract, the plasma Triglycerides levels were significantly decreased (P<0.005) and still dropped after 2 weeks (P<0.01).
On the other hand, the repeated oral administration of SP aqueous extract caused a significant decrease of body weight after 2 weeks of treatment in both normal (P<0.001) and diabetic (P<0.01) rats.
We conclude that the aqueous extract of SP exhibits acholesterol and body weight-lowering activities in both normal and severe hyperglycaemic rats.
Stigmasterol
In this study, incorporation of gallic acid into typical phytosterols (β-sitosterol and stigmasterol) through Steglich esterification was optimized employing the protection and deprotection strategy. A novel mechanism leading to side esterification was discovered. Complication of the phenolic hydroxyl groups and side reactions were successfully reduced under the optimized conditions. The structural identity and purity of galloyl stigmasterol and galloyl β-sitosterol were confirmed by NMR, FT-IR, and HPLC-MS. Evaluation of galloyl β-sitosterol and galloyl stigmasterol revealed their excellent antioxidant andcholesterol-reducing activities. Significant enhancement ofcholesterol-reducing activity by galloylation was unveiled especially for β-sitosterol. Galloyl β-sitosterol had slightly better antioxidant activity at ambient temperature and bettercholesterol-reducing activity. Molecular modeling suggested that a subtle difference of galloyl β-sitosterol and galloyl stigmasterol in activities could be attributed to variation of molecular rigidity and conformation. The excellent properties of galloyl β-sitosterol and galloyl stigmasterol suggested their great potential application in the food industry.
Stigmasterol and β-sitosterol, at a dose corresponding to that suggested for humans by the FDA for lowering cholesterol levels, are shown to alleviate HFWD-induced NAFLD. Stigmasterol was more effective than β-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels.
Suji leaf (Dracaena angustifolia Roxb.)
Activity Test of Suji Leaf Extract (Dracaena angustifolia Roxb.) on in vitrocholesterol lowering
cholesterol is a natural substance with physical characteristic similar to fat but has a steroidal group. The body requirescholesterol in normal amount; however, it will harm the body in excess amount.highcholesterol levels in theblood are dangerous because of the precipitation ofcholesterol and other fatty substances resulting inAtherosclerosis. Suji leaf (Dracaena angustifolia Roxb.) used as a natural dye has ahigh flavonoid content that is inferred to havecholesterol-lowering activity. This study aims to test the in vitro activity of suji leaf (Dracaena angustifolia Roxb.) extract in decreasingcholesterol level with various concentrations and to find theeffective concentration (EC50). The method of extraction used was remaceration method with 70% ethanol solvent. Analysis ofcholesterol-lowering activity was done by Lieberman-Burchard method by making variation of ethanol extract 400 ppm, 500 ppm, 600 ppm, 700 ppm, and 800 ppm. The results showed the percentage ofcholesterol-lowering activity by 33.62%, 36.15%, 46.61%, 56.39% and 64.05% respectively. Value of EC50 activity of suji leaf extract is 632.50 ppm.
Tanshinone ⅡA
The structure formula of TAN2A and its derivative TAN20 was finally determined and shown in Fig. 1A. Metabolic effects of TAN2A/TAN20 were evaluated by administering the compounds to db/db mice. After four weeks of TAN20 treatment, the weight of mice decreased significantly (p < 0.05), but no evidence for an effect of TAN2A was found (p > 0.05) (Fig. 1B). We found that serum Triglyceride levels decreased after TAN20 treatment (Fig. 1C).
taioba (Xanthosoma sagittifolium) leaf
The consumption of vegetables has been correlated with reduced risk of chronic non-communicable diseases due to thehigh fiber content and bioactive compounds found in vegetables. The arrowleaf elephant ear (Xanthosoma sagittifolium), which is known in Brazil as taioba, is a common plant in tropical America. Although its leafy portion possesses ahigh nutritional value, it is not widely consumed and has not been well studied. This study assessed theeffect of lyophilised taioba leaf (LTL) as ahypolipidemic and prebiotic agent. Thirty-two Wistar rats were assigned to four groups: group 1 was fed ahigh-fatdiet containing 3.67% (w/w) cellulose (low cellulose — LCEL); group 2 received ahigh-fatdiet supplemented with 10% (w/w) cellulose (CEL); group 3 received ahigh-fatdiet supplemented with 10% (w/w) inulin (INU); and group 4 was fed ahigh-fatdiet supplemented with 28.4% LTL (TAI) to provide 10% (w/w) taioba fiber. The groups were fed their respectivediets for 4 weeks. The addition of LTL to thediet resulted in reduced weight gain, reduced liver fat, and increased fecal mass andlipid, in addition tohigher fecal short chain fatty acid and bile salt concentrations, compared to the LCEL group. Additionally, only the TAI group exhibited a lowerserumcholesterol concentration and ahigher body ash content (p < 0.05) than the LCEL group. Both thehigh bile salt binding capacity andhigh fermentability of LTL suggest that this plant may have a protectiveeffect against cardiovascular diseases and bowel cancer.
Tangeretin
One of the pathways to reducecholesterol production in the liver is through the inhibition of HMG-Coa reductase (HMGCR) by current drugs, statins. However, these have sideeffects if consumed in prolonged periods. Tangeretin and trans-ethyl caffeate as alternative drugs inreducing hypercholesterolemia and preventingAtherosclerosis have never been reported. Theireffects on inhibiting HMGCR activity were investigated through enzymatic method (in vitro and in vivo). The toxicity property was analyzed on theserum Glutamate Oxalate Transaminase (SGOT)/serum Glutamate Piruvate Transaminase (SGPT) levels and rat liver histology. The results showed that both compounds inhibited HMGCR activity significantly compare to the control simvastatin (p < 0.05). Tangeretin which showed very good activity in inhibiting HMGCR (83.8 of % inhibition, equal to simvastatin) was selected and used for anti-hypercholesterolemia in vivo assessment. Furthermore, tangeretin was shown toeffectively reduced Totalcholesterol (TC) and Low Density Lipoprotein (LDL), and increasedhigh Density Lipoprotein (HDL) levels significantly compared to the simvastatin group (p < 0.05). Tangeretin group was also proven to inhibit HMGCR rat liver activity significantly compare to the control simvastatin (p < 0.05). The toxicity study on the SGOT/SGPT levels and liver histology revealed that there were no sideeffects after administration by tangeretin. Results found that both tangeretin and trans-ethyl caffeate are potent candidates as anti-hypercholesterolemia agent in vitro. In addition, tangeretin was also shown to be safe and suitable as an alternative treatment for controlling hypercholesterolemia in vivo as well as have potency for preventingAtherosclerosis.
Taxillus sutchuenensis (Lecomte) Danser extract
Bushenkangshuai tablet (BSKS) is a Chinese herbal compound which has been used for the treatment of cardiovascular and cerebrovascular diseases in China for decades. This study intends to explore the molecular mechanism of BSKS againstAtherosclerosis in ApoE−/− mice. ApoE−/− mice were fed with western-typediet for 6 weeks and then were given BSKS for 6 weeks. The results showed that BSKS attenuated the size of the atherosclerotic lesion, reduced visceral adipose content, and decreasedbloodlipids. We also found that BSKS promoted the expression of adiponectin and its receptors, inhibited the expression of Toll-like receptor 4 and nuclear factor-kappa B, decreased the levels of interleukin-1 beta, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1, and increased the levels of interleukin-10 and adiponectin. Our data provided evidence that BSKS exerted anAntiatheroscleroticeffect byloweringbloodlipids and inhibiting inflammatory response via TLR4 and NF-κB signaling pathway.
Teucrium polium L.
Background
Cardiovascular diseases are among the most common causes of mortality worldwide. Therefore, it is necessary to control the risk factors of these patients. Since the level of inflammatory markers andlipid profiles has increased in cardiovascular diseases and due to the increasing role of plants in the treatment of diseases, the current study aimed to investigate theeffect of hydroalcoholic extract of Teucrium polium on inflammatory markers andlipid profile in hypercholesterolemic rats.
Materials and methods
A total of 24 adult male Wistar rats were randomly divided into four groups of six each and treated with oral administration for 8 weeks. The control group received normaldiet, the sham group receivedhigh-cholesteroldiet and experimental groups 1 and 2 receivedhigh-cholesteroldiet in the 8 weeks and doses of 85 and 170 mg/kg, respectively, of the T. polium hydroalcoholic extract (TPHAE) in the second 4 weeks. At the beginning and the end of the study, rats were examined for biochemical parameters. The mean level of variables for each group was presented as mean ± standard error of mean.
Results
The results of this study showed that, after administration of TPHAE, there was a significant decrease in the mean of inflammatory markers in all groups compared to sham group (P<0.001). Also, administration of the extract significantly reduced theserum levels of Triglyceride ,cholesterol andLDL-cholesterol and significantly increased theserum HDL-cholesterol levels. In addition, the 170 mg/kg dose of TPHAE was the mosteffective inreducingserum levels of inflammatory andlipid markers.
Conclusion
Treatment with TPHAE caused dose-dependent decrease inserum levels of inflammatory markers andlipid profile in hypercholesterolemic rats. Therefore, it can be applied as a natural product for the management of cardiovascular diseases.
Thearubigins (from Black Tea)
Rats were fed ahigh fatdiet containing 0.2% black tea polyphenols, theaflavins, theasinensin A or thearubigins for 4 weeks. The hepaticcholesterol concentration was significantly lower in rats fed the theaflavins, theasinensin A or thearubiginsdiet than in those fed the controldiet without black tea polyphenols. Theasinensin A and thearubigins significantly accelerated fecal neutral and acidic steroid excretion, respectively. These results suggest that theasinensin A and thearubigins might induce the hepaticcholesterol-lowering activity through the promotion of fecal steroid excretion.
Theasinensin A (from Black Tea)
Rats were fed ahigh fatdiet containing 0.2% black tea polyphenols, theaflavins, theasinensin A or thearubigins for 4 weeks. The hepaticcholesterol concentration was significantly lower in rats fed the theaflavins, theasinensin A or thearubiginsdiet than in those fed the controldiet without black tea polyphenols. Theasinensin A and thearubigins significantly accelerated fecal neutral and acidic steroid excretion, respectively. These results suggest that theasinensin A and thearubigins might induce the hepaticcholesterol-lowering activity through the promotion of fecal steroid excretion.
Trigonella foenum-graecum L seed extract
Background.
Trigonella foenum graecum L. (Fenugreek, FG) is used in many countries as a medicinal plant. Evidence has suggested thehypolipidemiceffect of Fenugreek; however, its actual mechanism has not been determined yet.
Objectives.
The purpose of our research was to investigate theeffect of Fenugreek onlipid profile, liver histology andLDL receptor gene expression in male hamsters fed withhighcholesteroldiet.
Methods.
These animals were given normaldiet (ND),highcholesteroldiet (HCD: 2%cholesterol and 0.5% cholic acid added to ND), HCD supplemented with 2g and 8g fenugreek per 100g ND (HCD+FG2 and HCD+FG8) respectively for four weeks. At the end of treatment,serumlipids, lipoproteins and liver enzymes were measured. Finally,LDL receptor (LDLR) gene expression was determined in the liver of the studied animals using Real Time-PCR method and liver histological changes were evaluated by H&E staining method.
Results.
A significant reduction was observed inserum Triglyceride (p<0.01), totalcholesterol, low and very low densitycholesterol, aspartate and alanine transaminases in HCD+FG8 group (p<0.05) compared with HCD group, whileserum level of HDL-c (p<0.01) increased. In addition,LDLR gene expression in HCD+FG8 group increased 7.8 folds. The results confirm the protectioneffect of liver tissue in HCD+FG8 group against pathological changes. There was no significant change inLDLR gene expression in HCD+FG2 group. In conclusion, fenugreekameliorated dyslipidemia byup-regulation ofLDLR gene expression and can be used as a protective agent against hypercholesterolemia.
Alcoholic extract of Trigonella foenum graecum seeds [fenugreek seed extract (FSE)] was studied in triton-induced and high-fat diet–induced hyperlipidemia to evaluate antidyslipidemic effect. Plasma cholesterol (26.19%) and Triglycerides (36.6%) were found to be lowered by FSE maximum at a dose of 200 mg/kg body weight in triton-treated hyperlipidemic rats. Chronic feeding of FSE (200 mg/kg body weight) caused lowering in plasma and hepatic lipid levels by activating lecithin–cholesterol acyltransferase (47%), postheparin lipolytic activity (35%), Triglyceride lipase (34%), lipoprotein lipase (20.8%), and increased excretion of fecal bile acids (36%–45%). The FSE shows potent antioxidant activity in both in vitro and in vivo systems. It inhibited generation of superoxide anion and hydroxyl free radicals in both enzymatic and nonenzymatic systems significantly at 200 µM concentration. Furthermore, FSE normalizes the activities of antioxidant enzymes, that is, superoxide dismutase and catalase, and reduces plasma lipid peroxidation (33.9%), hepatic 4-hydroxynonenal (27%), and isoprostanes (28%). Data of the present study demonstrated that the T. foenum graecum seed extract has both antidyslipidemic and antioxidant properties.
Non-alcoholic steatohepatitis (NASH) is a severe variant of non-alcoholic fatty liver disease (NAFLD). It is characterized by the accumulation of fats such (as Triglyceride) that resulted in inflammation and ballooning in addition to steatosis (Ikura, 2022). NAFLD affects 25% of the adult population globally, 13.5% in Africa, and 31.8% in the Middle East
Typha angustifolia L.extract
Typha angustifolia extract reducesdiet-induced hyperlipidemia in rats
Objective
To observe thelipid-loweringeffect of Typha angustifolia extract (TAE) in Sprague Dawley rats.
Methods
The rats were randomly divided into six groups, including the hypercholesterolemicdiet (HYD) group. Ad libitum food was given to the animals for 60 d to establish dyslipidemia models. The rats were received an ig administration of 1 mL medicine daily. After 120 d the animals were sacrificed by cervical dislocation;blood was collected to measure totalcholesterol (TC), Triglycerides (TG), low-density lipoproteincholesterol (LDL-C),high-density lipoprotein-cholesterol (HDL-C), nitric oxide (NO), and endothelin (ET) plasma concentration; Livers were collected to measure ApoE mRNA and protein expression; Morphologic changes of aorta ventralis tissue were also observed.
Results
Compared with HYD group, TAE had the ability ofreducing TC, TG,LDL-C, NO, and ET (P < 0.01), thereby increasing ApoE mRNA and protein expression of the liver (P < 0.01).
Conclusion
These results suggested that TAE was capable ofeffectively decreasing the circulatinglipids levels and enhancing the protectiveeffects of artery.
Urolithin B
Scope
HDLcholesterol is inversely related to the incidence ofAtherosclerosis. Polyphenols including ellagitannins have been shown to exert antiatherogenic properties. Urolithin B is formed from ellagitannins by components of the gut microbiota, and urolithins might be involved in beneficialeffects against cardiovascular diseases in vitro. In this study, the influence of urolithin B on several parameters involved in thelipid plaque deposition and thereversecholesteroltransport is investigated.
Methods and results
In apoE−/− mice and two different macrophage cell lines, the influence of urolithin B and its phase II conjugated metabolite onlipid plaque deposition,cholesterol uptake, and expression of ABCA1 and SR-BI is tested. It is shown that urolithin B decreaseslipid plaque deposition, both urolithin B and urolithin B sulfate modulate expression of SR-BI and ABCA1, andcholesterolefflux increases fromcholesterol laden macrophages to HDL particles as well as toreverselipid uptake by stimulated THP-1 macrophages.
Conclusions
Urolithin B can decreaselipid plaque deposition, and urolithin B and urolithin B sulfate are able to inducereversecholesteroltransport by influencing expression of key proteins of this pathway. Urolithin B may represent the basis for development of new drugs for prevention and treatment ofAtherosclerosis in humans.
Urolithins (Uro) are ellagic acid (EA)-derived metabolites produced by gut microbes. There is a growing interest in the biological activities of Uro. Our aim was to evaluate the impacts of Uro on regulating Triglyceride (TG) accumulation using cultures of primary human adipocytes and hepatoma Huh7 cells.
Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet
Urolithins are gut microbiota-derived polyphenol metabolites, produced following the consumption of pomegranate, berries, and nuts. Recent studies have shown the potentials of these metabolites on reducing Triglycerides accumulation in cultured hepatocytes and adipocytes. In this study, we investigated the ability of both urolithin A (Uro-A) and urolithin B (Uro-B) to attenuate obesity and associated symptoms in a high-fat diet-induced obesity model in rats.
Ursodeoxycholic acid
Administration of ursodeoxycholic acid (UDCA) has been shown to decreaseserum total and low density lipoprotein (LDL)cholesterol in hypercholesterolemic patients with primary biliary cirrhosis. Results of previous studies prompted us to postulate that thecholesterol-loweringeffect of UDCA may be due, at least in part, to a direct increment in hepaticLDL receptor binding [Bouscarel et al., Biochem J, 1991;280:589; Bouscarel et al.,lipids 1995;30:607]. The aim of the present investigation was to determine the ability of UDCA to enhance hepatocellularLDL receptor recruitment, as determined by itseffect in vivo onLDL uptake, and itseffect in vitro onLDL binding, under conditions of moderately elevatedserumcholesterol. Study groups consisted of male golden Syrian hamsters fed either a standard chowdiet (control), a 0.15%cholesterol-containingdiet, or a 0.15%cholesterol-containingdiet supplemented with either 0.1% UDCA, or 0.1% chenodeoxycholic acid (CDCA).cholesterol feeding increased (P<0.01) totalserumcholesterol by 44%, and was associated with a 10-fold accumulation of cholesteryl esters in the liver (P<0.01). In vivo, hepatic uptake of [U-(14)C]sucrose-labeled hamsterLDL was increased (P<0.05) to a level of 454+/-101 microl in animals fed acholesterol-containingdiet supplemented with UDCA, compared to that either without UDCA (337+/-56 microl), or with CDCA (240+/-49 microl). The hepatic uptake of [U-(14)C]sucrose-labeled methylated humanLDL, a marker ofLDL receptor-independentLDL uptake, was unaffected by bile acid feeding. In vitro, specific binding of [125I]hamsterLDL to isolated hepatocytes was determined at 4 degrees C, in presence and absence of 700 micromol/l UDCA. The K(D) ranged from 25 to 31 microg/ml, and was not affected by eithercholesterol feeding or UDCA. In the presence of UDCA, the B(max) was increased by 19% (P<0.05) in cells isolated from control animals and by 29% (P<0.01) in cells isolated from hamsters fed acholesterol-supplementeddiet. In conclusion, indietary hypercholesterolemic hamsters, both chronic in-vivo and acute in-vitro treatments with UDCA resulted in restoration of hepaticLDL binding and uptake to levels observed in control hamsters.
cholesterol-loweringeffect of ursodeoxycholic acid in patients with primary biliary cirrhosis
We have previously shown in a 2-yr controlled trial that hypercholesterolemia, frequent in primary biliary cirrhosis, is lowered by ursodeoxycholic acid (13 to 15 mg daily). To further investigate thiseffect, we analyzed the influence of long-term ursodeoxycholic acid administration onserumlipids, lipoproteins and bile acids. The study involved a subgroup of 33 noncirrhotic patients (17 received ursodeoxycholic acid and 16 received a placebo) analyzed at inclusion and after 2 yr. The totalserumcholesterol concentration was markedly reduced in the ursodeoxycholic acid–treated patients in comparison with the controls (mean ± S.E.M. = 7.49 ± 0.42 mmol/L and 7.07 ± 0.23 mmol/L at entry and 4.44 ± 0.40 mmol/L and 6.89 ± 0.27 mmol/L at 2 yr in the ursodeoxycholic acid and placebo groups, respectively; p < 0.02). Quantitatively, this decrease was mainly caused by a fall in low-density–lipoproteincholesterol, but very low density–lipoproteincholesterol levels also fell significantly.high-density–lipoproteincholesterol levels remained stable in both groups, but thehigh-density–lipoprotein2/high-density–lipoprotein3cholesterol ratio fell significantly during ursodeoxycholic acid treatment. No significant change occurred in total Triglyceride or total phospholipid levels. In the treated group, the proportion of ursodeoxycholic acid increased (up to 60% of total circulating bile acids), whereas that of cholic and chenodeoxycholic acids fell significantly. In conclusion, thecholesterol-loweringeffect of ursodeoxycholic acid could be related to an improvement of cholestasis, modifications incholesterolmetabolism or both. Changes in endogenous bile acid composition induced by ursodeoxycholic acid might be the common denominator of these two mechanisms.
Hypercholesterolemia and hyperTriglyceridemia areoften observed in PBC patients. Although it remainscontroversial whether or not the lipid abnormalities inthis disease increase atherosclerotic risk, 49 the adminis-tration of bezafibrate significantly reduced the serumconcentrations of LDL cholesterol and Triglycerides.The mechanism of the cholesterol-lowering effect ofbezafibrate has not yet been completely elucidated, andat the very least, it is not likely due to a direct inhibitionof HMGCR 50 (Fig. 5C).
Vernonia amygdalina leave extract
We investigated thelipid-lowering effects of methanolic extract of Vernonia amygdalina (VA) leaves in rats fed anhighcholesteroldiet, and compared with a standardhypolipidemic drug, Questran (Qu). Theeffects of VA on thelipid profile were assessed by measuring the levels of totalcholesterol, Triglyceride , low-density lipoprotein (LDL)cholesterol,high-density lipoprotein (HDL)cholesterol,lipid peroxidation (LPO), phospholipid, and glutathione (GSH) in the plasma and liver of the rats. Administration ofcholesterol at a dose of 30 mg/0.3 ml, five times in a week for nine consecutive weeks resulted in a significant increase (p < 0.05) in plasma and post mitochondrial fraction (PMF)cholesterol levels by 33% and 55%, respectively. However, treatment with extract of VA at doses of 100 and 200 mg/kg caused a dose dependent reduction in the plasma and PMFcholesterol by 20%, 23% and 23%, 29%, respectively. Similar reduction incholesterol levels was obtained in Qu-treated rats. Furthermore, VA at 200 mg/kg decreased the plasma and PMFLDL-cholesterol levels by 23% and 49%, and also decreased plasma and PMF Triglyceride levels by 29% and 28%, respectively. Also, VA at 100 and 200 mg/kg caused a dose-dependent increase in plasma HDL-cholesterol levels by 41% and 59%, respectively. However, there were no significant differences (p > 0.05) in the PMF HDL-cholesterol and phospholipid levels of the treated rats when compared to hypercholesterolemic rats. There were significant decreases (p < 0.05) in the LPO levels of extract-treated rats. Precisely, VA at 100 and 200 mg/kg decreased the levels of plasma and PMF LPO by 38%, 42% and 35%, 45%, respectively. In addition, VA augmented thecholesterol-induced decrease in PMF glutathione levels of the rats. Taken together, these results suggest thelipid-lowering effects of VA and, probably serve as a new potential natural product for the treatment of hyperlipidemia.
Fasted blood samples were collected for estimation of fasting blood glucose (FBG); total cholesterol (TC), Triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C) using standard biochemical methods. Statistical analysis was carried out using Student’s t test, P<0.05 was considered significant. After treatment, there were significant decreases in levels of FBG, TC, TG, LDL-C but increase level of HDL-C of B, C, & D
Vitamin E nicotics
A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma Triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased Triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The Triglyceride– and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.
Wheat Germ extract
At the same time, Triglyceride and cholesterol accumulation in the liver and the Triglyceride content in skin were significantly decreased. When wheat germ was added to the low fat diet, cholesterol and Triglycerides were not significantly modified. No adaptative change in lipase and colipase contents was observed in the pancreas of rats fed the wheat germ-supplemented diets, whereas the high fat diet increased these values. The results show a beneficial effect of wheat germ added to a high fat-cholesterol diet on the lipid status of rats; the implicated mechanisms are yet to be elucidated.
White kidney bean extract α-amylase
The increased level of serum insulin should be the result by effects of the above factors. In addition, our study also found that serum TC, TG, LDL levels in the HFD group were significantly higher than those in normal mice, consistent with previous studies [11]. HDL levels in PVE and Y group were significantly higher than normal mice, and there was no significant difference in HDL concentrations between the two groups of mice. In the intervention groups, the PVE, Y, and PVE with yogurt significantly decreased mice cholesterol, Triglyceride, LDL cholesterol, and increased the high-density lipoprotein cholesterol, reduced lipid metabolism disorder, and gradually restored the blood lipid level of glycemic mice to the normal state. These results suggested that PVE as food additives in yogurt have potentials for anti-diabetic activity and play a positive role in dyslipidemia.
Wild chrysanthemum extract
In our previous study, we compared the effects of Chrysanthemum flavonoids (CF), luteolin, and luteoloside, on improving blood lipid and liver steatosis, and found that the preliminary mechanism may be related to antioxidant levels and enzymes related to regulating fatty acid, cholesterol, and Triglyceride metabolism in the liver (16). In this study, differential genes are screened out by a gene chip, and the molecular mechanism of their function is further discussed from the biological process and signal pathway.
Wogonin
Hence, FGF21 knockout mice showed impaired adaptation to cold exposure [6]. FGF21 has been shown to normalize plasma glucose, insulin, and Triglyceride levels in some type 2 diabetes mouse models [5,7]. Thus, it is a therapeutic target for metabolic diseases.
Xanthohumol
Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse cholesteroltransport
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increaseshigh-density lipoprotein (HDL)cholesterol levels. It is not clear whether xanthohumol promotesreversecholesteroltransport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated theeffects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [3H]-cholesterol-labeled macrophages. Ex vivo experiments were then employed to investigate the detailed mechanism by which xanthohumol enhanced RCT.cholesterolefflux capacity from macrophages was 1.5-foldhigher in xanthohumol-fed hamsters compared with the control group. In addition, protein expression and lecithin-cholesterol acyltransferase activity in the HDL fraction were significantlyhigher in xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions of liver X receptor α and bile pump export protein were increased in the liver by xanthohumol administration when compared with the control, implying that it stimulated bile acid synthesis andcholesterol excretion to feces. In conclusion, our data demonstrate that xanthohumol improves RCT in vivo throughcholesterolefflux from macrophages and excretion to feces, leading to antiAtherosclerosiseffects. It remains to be elucidated whether enhancement of RCT by xanthohumol could prove valuable in humans.
The Chalcone Xanthohumol Inhibits Triglyceride and Apolipoprotein B Secretion in HepG2 Cells
The present study examined the role of xanthohumol (XN), a plant chalcone, on apolipoprotein B (apoB) and Triglyceride (TG) synthesis and secretion, using HepG2 cells as the model system. The data indicated that XN decreased apoB secretion in a dose-dependent manner under both basal and lipid-rich conditions (as much as 43% at 15 μmol/L). This decrease was associated with increased cellular apoB degradation. To determine the mechanism underlying this effect, we examined Triglyceride availability, a major factor in the regulation of apoB secretion.
Total serum cholesterol (T-Cho), HDL-C and Triglyceride (TG) levels were measured every 6 weeks, using test-Wako kits (Wako Pure Chemicals). To prepare the HDL fraction, serums were mixed with an equal volume of 13% polyethylene glycol 6000 (PEG, Wako Pure Chemicals) before centrifugation (8000 g, 10 min, room temperature) [9]. We confirmed that the supernatants contained HDL and apoE-rich HDL by lipoprotein electrophoresis (Figure S1). Lipoprotein electrophoresis for sera and HDL-fractions were performed using agarose gel (Helena Laboratories, Texas, USA) with barbital buffer. Cholesterol and cholesterol ester were enzymatically stained.
XN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic Triglyceride and cholesterol content, activation of AMP-activated protein kinase, phosphorylation and inactivation of acetyl-CoA carboxylase, and reduced expression levels of mature sterol regulatory element-binding protein (SREBP)-2 and SREBP-1c mRNA indicate reduced lipogenesis in the liver of XN-fed ApoE−/− mice.
Xuezhikang
Background: Xuezhikang (XZK) is an extract of fermented red yeast rice that haslipid-lowering properties.
Objective: To evaluate theeffects of XZK onlipids in subjects with dyslipidemia but no coronary heart disease.
Methods: A total of 116 adults with baseline non-high-density lipoproteincholesterol (non-HDL-C) levels of approximately 208 mg/dL and low-density lipoproteincholesterol (LDL-C) levels of approximately 175 mg/dL were randomized to either placebo or XZK 1200 or 2400 mg daily and treated for 12 weeks.
Results: A majority of the patients were white (53.4%) or Asian (37.1%). Daily XZK 1200 mg and 2400 mg for 4 to 12 weeks resulted in statistically significant (P < .001) and clinically meaningful decreases in non-HDL-C (∼24% reduction) andLDL-C (∼27% reduction) compared with placebo. XZK treatment at either dose enabled approximately 50% of subjects to reduce theirLDL-C levels by ≥ 30%. Doubling the XZK daily dose from 1200 to 2400 mg at treatment week 8 caused an additional 4.6% reduction inLDL-C. Significant benefits were also observed across secondary efficacy variables, including totalcholesterol (TC),apolipoprotein B (Apo B), Triglycerides , HDL-C, the TC/HDL-C ratio, and the Apo B/Apo A-I ratio, at treatment week 8 or 12. XZK was safe and well tolerated. Safety and tolerability profiles were similar across treatment groups. Most adverse events were gastrointestinal. No subject experienced myopathy or markedly elevated liver transaminases or creatine kinase.
Conclusion: Xuezhikang significantly reduced non-HDL-C andLDL-C, and was well tolerated. Further, longer-term studies in more diverse patient populations are needed to corroborate these findings.
Xuezhikang (XZK), an extract of Chinese red yeast rice, is recommended as an optimal choice for patients with coronary heart disease (CHD) with markedly elevated Triglyceride (TG) levels. This study was designed to compare the hypoTriglyceridemic effects between XZK and simvastatin. The role of apolipoprotein A5 (apoA5), a key regulator of TG metabolism and a target gene of peroxisome proliferator-activated receptor α (PPARα), was to be identified in XZK-related hypoTriglyceridemic actions.
Endothelial dysfunction is associated with inflammation and postprandial hyperTriglyceridemia. Xuezhikang, an extract of Cholestin, a dietary supplement, has lipid-modulating and antiinflammatory effects. We explored the effects of xuezhikang on endothelial function and high-sensitivity C-reactive protein (hs-CRP) in patients with coronary heart disease (CHD).
Yucca schidigera extact
Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review
Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatoryeffects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biologicaleffects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory activity. They areInhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthriticeffects of Yucca schidigera are warranted.
Zingiber officinale Roscoe extract
Background & aims
Hypertension, dyslipidaemia, and chronic inflammation contribute to the development of cardiovascular disease (CVD). Zingiber officinale has been suggested to reduce these CVD risk factors; however, the clinical evidence remains unclear. This systematic review aims to analyse theeffect of Z. officinale as a sole intervention on these risk factors.
Methods
In this PRISMA-based systematic review, we included randomised clinical trials from PubMed, Scopus and Cochrane Database of Systematic Reviews (July 2020) analysing Triglycerides , low- andhigh-density lipoprotein (LDL, HDL), totalcholesterol, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin 1, 6, 10, systolic and/or diastolicblood pressure as outcomes. Quality of studies was evaluated by JADAD and the Cochrane risk-of-bias tools.
Results
A total of 24 studies were included, mostly (79.2%) showing low risk of bias. These were based on obesity and cardio-metabolic derangements (33.3%), type 2 diabetes mellitus (37.5%), and miscellaneous conditions (29.2%). While totalcholesterol and Triglycerides levels mostlyimproved after Z. officinale, results were inconsistent for otherbloodlipids markers. Inflammatory markers (CRP, TNF-α) were more consistently reduced by Z. officinale, while only 3 studies reported a non-significant reduction ofblood pressure.
Conclusions
Although there remains a paucity of studies, Z. officinale may be beneficial for improving dyslipidaemia and inflammation.
Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic syndrome: a review
In recent years, metabolic syndromes (MetSs), including diabetes mellitus, dyslipidemia, and cardiovascular diseases, have become a common health problem in both developed and developing countries. Accumulating data have suggested that traditional herbs might be able to provide a wide range of remedies in prevention and treatment of MetSs. Ginger (Zingiber officinale Roscoe, Zingiberaceae) has been documented to ameliorate hyperlipidemia, hyperglycemia, oxidative stress, and inflammation. These beneficial effects are mediated by transcription factors, such as peroxisome proliferator–activated receptors, adenosine monophosphate–activated protein kinase, and nuclear factor κB. This review focuses on recent findings regarding the beneficial effects of ginger on obesity and related complications in MetS and discusses its potential mechanisms of action. This review provides guidance for further applications of ginger for personalized nutrition and medicine.
Regarding the results of the present study, the levels of biochemical parameters including blood glucose, total cholesterol(TC),Triglycerides (TG), low-density and very low-density lipoprotein (LDL, VLDL), urea and creatinine, in addition to the liver enzymes activity of AST, ALT and ALP all showed a significant increase (P˂ 0.05) at the treated group with alloxan and the amaryl group, on the contrary, the levels of high-density lipoprotein (HDL) revealed significant decrease(P˂ 0.05) in the same two groups, while the groups that were dosed with the terpene extract in two concentrations (150 and 300) mg /kg revealed notable decrement (P˂ 0.05 ) in the levels of total cholesterol (TC), Triglycerides (TG), and low-density and very low-density lipoprotein (LDL, VLDL), in addition to the liver enzymes activity of AST, ALT and ALP, also levels of urea and creatinine, contrastively, the levels of HDL showed a observable elevation (P˂ 0.05) in the group that administrated with terpene at concentration of 300 mg ⁄ kg when compared with the control group and other experimental groups.
α-Lipoic Acid
To investigate thecholesterol-loweringeffectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4diets for 30 days: (i)high fatdiet (HF, 40% energy from fat); (ii) HFdiet supplemented with 3% phytosterols; (iii) HFdiet supplemented with 0.25% αLA; or (iv) HFdiet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HFdiet, combination PS/αLA proved moreeffective inreducing non-HDLcholesterol (−55%) than either the PS (−24%) or the αLA (−25%) therapies alone. PS supplementation did not affectLDL particle number, however, αLA supplementation reducedLDL particle number when supplemented alone (−47%) or in combination with PS (−54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21–22%). PS-mediated interruption of intestinalcholesterolabsorption was evident by increased fecalcholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecalcholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects ofcholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increasedcholesterol clearance (reducedPCSK9 mRNA, 0.5 fold of HF; increasedLDLR protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensivecholesterollowering response than either therapy alone.
lipidlowering effect of Antioxidant Alpha-Lipoic Acid in ExperimentalAtherosclerosis
Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development ofAtherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1%cholesterol richdiet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks.blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared forlipid profile estimation and microsomallipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma totalcholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction oflipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a duallipidlowering andAnti-atherosclerotic properties indicated with low plasma TC andLDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits.
Considering the current obesity epidemic in the United States (>100 million adults are overweight or obese), the prevalence of hyperTriglyceridemia is likely to grow beyond present statistics of ∼30% of the population. Conventional therapies for managing hyperTriglyceridemia include lifestyle modifications such as diet and exercise, pharmacological approaches, and nutritional supplements. It is critically important to identify new strategies that would be safe and effective in lowering hyperTriglyceridemia. α-Lipoic acid (LA) is a naturally occurring enzyme cofactor found in the human body in small quantities. A growing body of evidence indicates a role of LA in ameliorating metabolic dysfunction and lipid anomalies primarily in animals. Limited human studies suggest LA is most efficacious in situations where blood Triglycerides are markedly elevated.
β-Sitosterol
Following 12 weeks of feeding, the rats were fasted overnight, weighed, and then euthanized. Plasma cholesterol, insulin, glucose, Triglyceride, and adiponectin concentrations were determined. Visceral fat was dissected out and weighed. The high-fructose diet increased (P < .05) visceral adiposity and plasma Triglyceride concentration but decreased (P < .05) plasma adiponectin concentration. β-sitosterol prevented the high-fructose diet-induced visceral obesity, hyperTriglyceridemia, and hypoadiponectinemia. β-sitosterol alone increased plasma adiponectin concentration and reduced plasma insulin concentration and homeostatic model assessment index. In conclusion, β-sitosterol could be potentially used to prevent high-fructose diet-induced metabolic dysfunction.
γ－aminobutyric acid (GABA)
The present study aims to investigate the effect of γ-aminobutyric acid (GABA) on liver lipid metabolism and on AA broilers. Broilers were divided into three groups and fed with low-fat diets, high-fat diets, and high-fat diets supplemented with GABA. Results showed that GABA supplementation decreased the level of Triglyceride (TG) in the serum and liver of broilers fed high-fat diets, accompanied by up-regulated mRNA expression of genes related to lipolysis and β-oxidation in the liver (p < 0.05). Furthermore, GABA supplementation increased liver antioxidant capacity, accompanied by up-regulated mRNA expression of antioxidant genes (p < 0.05). 16S rRNA gene sequencing showed that GABA improved high-fat diet-induced dysbiosis of gut microbiota, increased the relative abundance of Bacteroidetes phylum and Barnesiella genus, and decreased the relative abundance of Firmicutes phylum and Ruminococcus_torques_group and Romboutsia genus (p < 0.05).
