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THROMBOLYTIC : Blood Clot Destroyer 200:1
$275.00
Introducing
THROMBOLYTIC
blood clot DESTROYER
200:1 Concentration
Featuring: Achyranthes Bidentata Bl. Root Extract • Aconitum Carmichaelii Debx. Root Extract • Acori Tatarinowii Rhizoma Extract • Albizia Richardiana Stem Extract • Alstonia Scholaris (L.) R. Br. Leaf Extract • Angelica Sinensis (Oliv.) Diels Root Extract • Anogeissus Latifolia Leaf Extract • Asparagi Radix Extract • Astragalus Membranaceus (Fisch.) Bge. Extract • Aucklandia Costus • Averrhoa Bilimbi (Oxalidiaceae) • Azadirachta Indica • Breviscapine • Bupleurum Chinense Dc. Extract • Carthamus Tinctorius FLOWer Extract • Chaenomeles Sinensis (Thouin) Koehne Extract • Cinnamomum Cassia Presl. Extract • Citrus Assamensis Leaf Extract • Citrus Aurantium L. Extract • Clerodendrum Viscosum (Verbanaceae) • Coicis Semen Extract • Cordycepin • Cordyceps Sinensis (Berk.) Sacc Extract • Curcumae Radix Extract • Cyathula Officinalis Kuan • Cyathulae Radix Extract • Dimocarpus Longan Lour. Extract • Dragon’s Blood From Dracaena Cochinchinensis (Lour.) S.C. Chen • Drynaria Quercifolia (Polypodiaceae). • Egb 761 From Ginkgo Biloba Extract • Epimeredi Indica (L.) Rothm • Evodia Rutaecarpa (Juss.) Benth Extract • Ganoderma Lucidum • Gastrodiae Rhizoma Extract • Haliotis Diversicolor Reeve Extract • Hawthorn Berry – Crataegus Laevigata • Kaempferol • Lagerstroemia Speciosa Leaf Extract • Leonurus Japonicus Sweet Extract • Licorice Root Extract -Glycyrrhiza Glabra L. • Ligusticum Chuam.Iong Hort.Extract • Lonicerae Japonicae Flos Extract • N-Acetylcysteine • Nattokinase • Nelumbinis Plumula Seed Extract • Nigella Sativa (L.) Seeds • Paeonia Suffruticosa Andr. Peel Extract • Paeonia Veitchii Lynch Root Extract • Panax Ginseng • Panax Notoginseng (Burk.)F. H. Chen Root Extract • Polygonum Multiflorum • Polygonum Tinctorium • Poria Cocos( Schw.) Wolf Extract • Pterocarpus Mildbraedii Harms Leaf Extract • Pueraria Lobata(Willd.)Ohwi Extract • Rehmanniae Radix Extract • Rutin • Salvia Miltiorrhiza Bge.Root Extract • Sargentodoxa Cuneata (Oliv.) Rehd. Et Wils. Extract • Sophora Japonical. Extract • Spirulan • Stevia Rebaudiana Leaf Extract • Taxillus Chinensis (Dc.) Danser.Extract • Tetracera Sarmentosa (L.) Vahl • Typha Angusti Folial Extract • Vitamin B6 • White Willow (Salix Alba)
POLYPHENOLS TO TREAT & PREVENT COVID-19
PREVENTING BLOOD CLOTS WITH FLAVONOIDS & POLYPHENOLS
Anti-thrombotic activity of plant extracts
INGREDIENTS & SCIENTIFIC STUDIES:
Achyranthes bidentata Bl. root extract
Achyranthes bidentata Bl. (A. bidentata) occupies an important position in traditional Chinese medicine owing to the property of promoting the circulation of blood and removing stasis. Achyranthes bidentata polypeptide k (ABPPk) is one of the active components isolated from A. bidentata. We previously demonstrated that ABPPk has potent neuroprotective effects against neuronal apoptosis both in vitro and in vivo, but the roles and mechanisms of ABPPk on long-term functional recovery after Ischemic Diseases Stroke remain unknown. In the current study, we investigated the neuroprotective effects of ABPPk on filament transient middle cerebral Artery occlusion (tMCAO) rats and found that ABPPk reduced the infarct volume and maintained the neuronal integrity in the Ischemic Diseases penumbra.
Moreover, we found that ABPPk might reduce the formation of downstream microthrombus through preventing Ischemic Diseases -induced oxidative damage of brain endothelial cells and activation of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), and NF-κB. ABPPk also inhibited polymorphonuclear leukocytes (PMNs) infiltration and matrix metalloproteinase-2/-9 (MMP-2/-9) activation in the Ischemic Diseases penumbra. Morris water maze, foot fault test, and modified neurological severity score were assessed for a period of 6 weeks following tMCAO. ABPPk improved long-term recognition abilities and neurological outcomes after Stroke compared with saline-treated rats. Taken together, these results suggested that ABPPk is beneficial to the improvement of long-term outcomes after transient cerebral ischemia injury and can be used as a potential neuroprotective agent .
Aconitum carmichaelii Debx. root extract
Ethnopharmacological relevance: The processed lateral root of Aconitum carmichaelii Debeaux (Ranunculaceae), an extensively used traditional Chinese medicine, is known as Fuzi in China (Chinese: 附子), “bushi” in Japan, “Kyeong-Po Buja” in Korea, Chinese aconite, monkshood or Chinese wolfsbane. It has been used to treat shock resulting from acute Myocardial Infarction , low blood pressure, Coronary Heart Disease , chronic Heart failure, etc.
Aim of the review: The present paper aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and toxicity of Fuzi. Besides, the possible tendency and perspective for future research of this plant are discussed, as well.
Materials and methods: All available information on Fuzi was collected via electronic search (using Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, and Web of Science), books and classic works about Chinese herb.
Results: 122 chemical constituents, among which C19-diterpenoid alkaloids and C20-diterpenoid alkaloids are the predominant groups, have been isolated and identified from Fuzi. Fuzi with its active compounds is possessed of wide-reaching biological activities, including effects on Cardiovascular system, anti-inflammation and analgesic action, anti-tumor activity, effect on the immune system, hypoglycemic and hypolipidemic effects , anti-aging effect, effect of protecting kidney and effect on energy metabolism.
Conclusions: Nearly all of compounds were found from the roots of the plant, so further phytochemical studies should focus more on the other parts of the plant, such as the leaves, flow ers or stems. Besides, a majority of the pharmacological studies were carried out using crude and poorly characterized extracts. Thus, more bioactive components particularly cardiotonic and analgesic compounds should be identified through bioactivity-guided isolation strategies. Moreover, investigations on how to develop Fuzi׳s new clinical usage on the basis of its pharmacological effects are in requirement.
Acori Tatarinowii Rhizoma extract
We investigated the antithrombotic effect of Acorus gramineus Soland (A. gramineus) from Korea and Acorus tatarinowii Schott (A. tatarinowii) from China in a rat model of Arterial Thrombosis induced by ferric chloride (). Thirty minutes prior to a 35% application, Sprague Dawley rats were intraperitoneally injected with saline, A. gramineus and A. tatarinowii (100 mg/kg), respectively. Occlusion time of rats injected with A. gramineus was delayed significantly compared to that of the vehicle and A. tatarinowii. thrombus weight was meaningfully decreased in rats injected with A. gramineus compared to the vehicle.
Additionally, A. gramineus inhibited collagen fiber damage in vessel compared to the vehicle, but A. tatarinowii did not show a significant effect. Our results show that A. gramineus and A. tatarinowii from the same genus have different antithrombotic effects , and especially A. gramineus has a better antithrombotic effect than A. tatarinowii.
effects of Acori Rhizoma Extract on the in vitro anti-platelet Activity in Human Whole blood
Objectives: Acori Rhizoma is one of the common widely used herbal medicines with diverse bioactive effects . However, little evidence has been reported about the potential anti-platelet activity of Acori Rhizoma. The present study examined the effects on platelet aggregation by Acori Rhizoma.
Methods: In this study, we tested the in vitro effect of 16 kinds of Acori Rhizoma extracts by hot water or 70% ethanol on collagen-induced platelet aggregation in human whole blood using the impedance method of aggregometry.
Results: Among them, 2 kinds of 70% ethanol extract and 1 kind of hot water extract showed the significant inhibiting effect on whole blood aggregation . In particular, Acorus gramineus extracts were selected as the most effective candidate.
Conclusions: The results from this experiment provide pharmacological evidence for the traditional medicine, suggesting that Acorus gramineus could be help problems of blood circulation more than Acorus tatarinowii.
Alstonia scholaris
Alstonia scholaris (L.) R.Br. is a medicinal herb belonging to the family Apocyanaceae. Locally it is known as Chatim and abundant with ethno-medicinal properties . The crude ethanolic extract of A. scholaris leaves along with its n-hexane, ethyl acetate, dichloromethane and aqueous soluble partitionates were assayed for their probable Thrombolytic and membrane stabilizing activities.
The activities of the leaf extract were compared to standard drugs, streptokinase for Thrombolytic and acetyl salicylic acid for membrane stabilizing activities. In this study, among all extractives the highest Thrombolytic activity was exhibited by the crude ethanolic extract (55.33±0.08%) (p < 0.001) as compared to Streptokinase (62.07±0.33%) (p < 0.001).
Alternatively, ethanol soluble materials also significantly inhibited the haemolysis of human erythrocyte membrane both in induced by hypotonic solution (83.47±0.15%) (p < 0.001) and by heat (79.82±0.71%) (p < 0.001), respectively as compared to standard acetyl salicylic acid (85.09±0.8%) (p < 0.001) and (80.98±1.34%) (p < 0.001).
Mechanisms underlying the antihypertensive effect of Alstonia scholaris
Ethnopharmacological relevance: Alstonia scholaris has a long history of use in the Ayurveda traditional treatment of various ailments including hypertension . We have reported the blood pressure lowering activity of the extract of A. scholaris. The following research aim to delineate the pharmacological mechanism involve in the antihypertensive action.
Materials and method: Vasorelaxant effect of the n-butanol fraction of A. scholaris (NBF-ASME) was evaluated on rat aorta pre-contracted with phenyelphrine (PE, 1 µM). Aortic rings preparation were pre-incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ 10 μM), methylene blue (MB 10 μM), Nω-nitro-L-arginine methyl ester hydrochloride (l-NAME 10 μM), atropine (10 μM), indomethacin (1 μM), ML-9 and various K+ channel blockers such as glibenclamide (10 μM) and tetraethyl ammonium (TEA 10 μM) for mechanism study.
Results: The results showed that pre-incubation of aortic rings with the extract (0.5, 1 and 2 mg/mL) significantly inhibit the contractile response of the rings to phenylephrine-induced contraction (p<0.05–0.001). Removal of endothelium, incubation with l-NAME, indomethacin, atropine and propranolol did not significantly affect the relaxation effect of NBF-ASME. Furthermore, the K+ channel blockers, TEA and glibenclamide showed no inhibitory effect. However, aortic rings pretreated with ODQ and ML-9 showed a significant suppression of the relaxation curve of NBF-ASME (p<0.01–0.001). In Ca2+-free solution, NBF-ASME inhibits the release of intracellular Ca2+ from the sarcoplasmic reticulum. NBF-ASME also inhibits calcium chloride (CaCl2)-induced contraction in endothelium-denuded aortic rings.
Conclusion: The results from this study suggests that A. scholaris exerts vasodilation via calcium channels blockade, direct activation of soluble guanylate cyclase and possibly by also inhibiting the formation of inositol 1, 4, 5-triphosphate.
Angelica sinensis (Oliv.) Diels root extract
antithrombotic therapy has become an important goal for the treatment of Ischemic Diseases disorders such as cerebral ischemia . Our recent studies found that Z-ligustilide (LIG), a characterized 3-n-alkylphthalide constituent of Radix Angelica sinensis essential oil, exerted significant neuroprotection against cerebral Ischemic Diseases damage in several animal models. The present study evaluated the antithrombotic activity of LIG and its effect on platelet aggregation and Coagulation time. LIG (10 or 40 mg/kg) was intragastrically administered to rats once daily for 3 days. Our results showed that LIG significantly and dose-dependently reduced Arterial thrombus weight in an arterioVenous shunt Thrombosis in rats and platelet aggregation induced by adenosine diphosphate in rats ex vivo. Meanwhile, LIG at 10 or 40 mg/kg had no significant effect on Coagulation time, including activated partial thromboplastin time and prothrombin time, in rats ex vivo. The present study demonstrated for the first time that LIG may exert efficient antithrombotic activity through inhibition of platelet aggregation , without effecting Coagulation time of peripheral blood. These data, together with the previously reported neuroprotective effects of LIG on cerebral ischemia , suggest that the antithrombotic activity of LIG may contribute to its potential for the treatment of Ischemic Diseases Diseases , including Ischemic Diseases Stroke .
Polysaccharides from Angelica sinensis alleviate neuronal cell injury caused by oxidative stress
Angelica sinensis has antioxidative and neuroprotective effects . In the present study, we aimed to determine the neuroprotective effect of polysaccharides isolated from Angelica sinensis. In a preliminary experiment, Angelica sinensis polysaccharides not only protected PC12 neuronal cells from H2O2-induced cytotoxicity, but also reduced apoptosis and intracellular reactive oxygen species levels, and increased the mitochondrial membrane potential induced by H2O2 treatment. In a rat model of local cerebral ischemia , we further demonstrated that Angelica sinensis polysaccharides enhanced the antioxidant activity in cerebral cortical neurons, increased the number of microvessels, and improved blood flow after ischemia . Our findings highlight the protective role of polysaccharides isolated from Angelica sinensis against nerve cell injury and impairment caused by oxidative stress.
Medicinal plants with antithrombotic property in Persian medicine: a mechanistic review
Thrombosis is one of the major causes of morbidity and mortality in a wide range of vessels Diseases . Due to the high prevalence of Thromboembolic disorders investigations are being carried out on new antithrombotic agents with limited adverse side effects in which herbal medicines are considered as alternative remedies. Persian medicine (PM) as a traditional medicine has a good potential for pharmacotherapy based on its own principles and development of drugs via investigating PM literature. In PM manuscripts there are some concepts that express the management of blood Clots and antithrombotic properties.
This study reviewed the pharmacological effects of medicinal plants mentioned in PM literature for blood Clot management in light of current knowledge. Plants mentioned in PM for management of blood Clot belong to 12 families in which Apiaceae, Lamiaceae and Compositae were the most repeated ones. Among the proposed plants Allium sativum, Rosmarinus officinalis, Boswellia serrata, Sesamum indicum, Matricaria chamomilla and Carthamus tinctorius have been the most researched plants in modern antithrombotic studies while for some plants such as Helichrysum stoechas, Dracocephalum kotschi, Carum carvi, Bunium persicum and Lagoecia cuminoides no evidence could be found. One of the interesting notes in Clot management in PM texts was introducing the target organ for some of the recommended herbs like Carum carvi and Bunium persicum for dissolving blood Clot in stomach and Commiphora mukul for thrombosed hemorrhoid.
It seems review of PM recommendations can help to design future researches for antithrombotic drugs discovering with more effectiveness and safety.
Anti-coagulant activity of plants: mini review
Medicinal plants have been used for treatment of human ailments since ancient times. Objective of this study is to document the effect of herbal drugs on Anticoagulant therapy. The material for this review was taken mostly from PubMed and the Cochrane database of systematic reviews. Some other relevant references were collected from personal database of papers on anti-coagulant properties of plants.
Literature review shows that many plants such as Thymus vulgaris, Cyamopsis tetragonoloba taub, Pulmonaria officinalis and Cinnamomum cassia etc have anti-coagulant activity. This review shows that medicinal plants should be prescribed with care to patients on Anticoagulant therapy.
Stroke therapy in traditional Chinese medicine (TCM): prospects for drug discovery and development
Brain injuries resulting from Stroke are a major and increasing public health problem in both developed and developing countries worldwide. China’s extensive experience in the use of traditional Chinese medicines (TCMs) in Stroke therapy indicates that TCM preparations are effective, with few or no side-effects . There are more than 100 traditional medicines in use for Stroke therapy in China. Some of their therapeutic effects in Stroke have been confirmed by recent clinical studies. A large number of compounds have been isolated from TCMs and most of these resources have not yet been characterized for pharmacological purposes.
Here, this article explains how TCM provides an extensive and knowledge-rich foundation for implementing a strategically focused pharmacological research programme aimed at the development of new drugs.
Overview of therapeutic potentiality of Angelica sinensis for Ischemic Diseases Stroke
Background: Ischemic Diseases Stroke is a common cerebrovascular Disease . Due to sudden interruption of blood flow by Arterial thrombus, amounts of neurons in Ischemic Diseases central and penumbral regions occur necrosis and apoptosis resulting in serious injury of neurological function. Chinese medicines have a great advantage in Ischemic Diseases Stroke treatment and recovery, especially Angelica sinensis.
Purpose: There are a large number of studies reported that Angelica injection and A. sinensis active compounds. We systematically reviewed the effects and mechanisms of A. sinensis in recent years according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements, and excavated its therapeutic potentiality for exploring more effective and safe compounds for Ischemic Diseases Stroke precision treatment.
Results: A. sinensis extracts and active compounds, such as Z-ligustilide, 3-n-Butylphthalide, and ferulic acid have significant effects of anti-inflammation, anti-oxidative stress, angiogenesis, neurogenesis, anti-platelet aggregation, anti-atherosclerosis, protection of vessels, which contributes to improvement of neurological function on Ischemic Diseases Stroke.
Conclusion: A. sinensis is a key agent for Ischemic Diseases Stroke treatment, and worth Deeply excavating its therapeutic potentiality with the aid of pharmacological network, computer-aided drug design, artificial intelligence, big data and multi-scale modelling techniques.
Albizia richardiana
Background: Albizia richardiana belongs Fabaceae family which different parts like fruits, flow ers, barks, and roots are used medicinally. The study reports the in vitro anti-inflammatory, Thrombolytic, cytotoxicity and antimicrobial activity of methanolic extract of A. richardiana stem and its different fractions.
Method: The methanolic extract of A. richardiana stem (MEAR) extracted with n-hexane (HXFAR), carbon tetrachloride (CTFAR), chloroform (CFAR), and aqueous (AQFAR) and subjected for DPPH scavenging activity and total phenol content (TPC). The cytotoxic activity evaluated by brine shrimp lethality bioassay, while the disk diffusion method used for the antimicrobial study. The anti-inflammatory and Thrombolytic activities of the extracts evaluated by the hypotonic solution induced hemolysis, heat-induced hemolysis and human blood Clotlysis, respectively.
Results: All the extracts exhibited excellent antioxidant activity in the DPPH scavenging assay and maximum total phenol content observed by HXFAR. Secondly, the extract showed a moderate LC50 value in brine shrimp lethality bioassay, where the CTFAR extract exhibited potential antimicrobial activities against sixteen different microorganisms. In anti-inflammatory, all the extract exhibited a significant (P < 0.0001) protection against lysis of human erythrocyte membrane induced by heat and hypotonic solution, as compared to the standard acetyl salicylic acid. An extremely significant (P < 0.0001) Clotlysis was found in MEAR (16.66%) while the standard drug streptokinase (70.94%).
Conclusion: All the fractions revealed the significant free radical scavenging activity. Moreover, CTFAR showed wide spectrum of antimicrobial activity. Thus, the results of the present study provided scientific evidence for the use of Albizia richardiana as traditional medicine.
Anogeissus latifolia leaf extract
IN-VITRO Thrombolytic POTENTIAL OF LEAF EXTRACT OF
ANOGEISSUS LATIFOLIA
Thrombotic disorders such as Myocardial Infarction and cerebral impediment are fatal blood Clotting related Diseases . The need of safer and reliable herbal medicines for targeted and better drugs is the need of the time, since the Thrombosis may further lead to complex blood dyscrasias. Thus the current study is targeted at exploration of the Thrombolytic potential of the hydro alcoholic leaf extract of indigenous herb Anogeissus latifolia. The plant has shown presence of phytoconstituents such as tannins, polyphenols which has been reported to show good cardio protective activity. Also, the plant has reported to show antihyperlipidemic activity, good anti-oxidant and anti-atherosclerosis activity.
Hence the plant promises to show fair Thrombolytic potential. Streptokinase was used as the standard drug for comparison and the saline solution as vehicle control. The plant has shown significant activity compared to both the groups.
Asparagi Radix extract
Anti-Thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs
The anti-Thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW) were investigated. Water extracts, a 70% methanol (MeOH) extract and an ethyl acetate (EtOAc) soluble fraction (III) from DJW inhibited platelet -activating factor (PAF)-induced platelet aggregation in vitro and in vivo assays. The extracts of DJW and eleven herbs from which it is derived, except for Panax ginseng Meyer, Angelica sinensis (OLIV.) DIELS and Schisandra chinensis Baill, inhibited AA-induced blood platelet aggregation to various extents.
The effects observed with total DJW was synergistic over-additive rather that additive since the sum of single contributions was lower than the effect of the total extract. Fraction III was specially protected against the lethality of PAF, while verapamil did not afford any protection. Exogenously applied arachidonic acid (AA) (100 μM) led to a 89% platelet aggregatio , the release of 14 pmol of ATP, and the formation of either 225 pg of thromboxane A2 (TXA2) or 45 pg of prostaglandin E2 (PGE2), each parameter being related to 106 platelet s. An application of DJW 5 min before AA, dose-dependently diminished aggregation, ATP-re lease, and the synthesis of TXA2 and PGE2, with IC50 values of 70, 87, 65 and 72 μg/ml, respectively.
The similarity of the IC50 values suggests the inhibition of cyclooxygenase (COX) by DJW as the primary target, thus suppressing the generation of TXA2, which induces platelet aggregation and the exocytosis of ATP by its binding on TXA2-receptors. These results indicate that DJW shows anti-thrombotic action on human platelets and inhibits the action of PAF in vivo by an antagonistic effect on PAF. Therefore, it may be useful in treating disorders caused by PAF.
Astragalus membranaceus(Fisch.)Bge.extract
The purpose of the study was to evaluate the effect of Astragalus membranaceus extract and ligustrazine combination on ameliorating inflammation in cerebral Ischemic Diseases rats that have undergone thrombolysis . Astragalus membranaceus and ligustrazine per se, or a combination of A. membranaceus and ligustrazine was administered by intraperitoneal injection immediately after surgery and sham surgery. After the induction of thrombolysis, the neurological function was measured and cerebral lesion volume was determined. The regulatory T cells in the spleen were measured by flow cytometry. To explore the protective effects of the combination drug on the neurological function and inflammation, the expression of transcription factor Foxp3 and cytokines, including transforming growth factor beta 1, interleukin 10, interleukin 4, interleukin 1 beta, interferon gamma, interleukin 17, in damaged brain was examined using reverse transcription polymerase chain reaction,
Western blot, and enzyme-linked immunosorbent assay. The cerebral lesion volume was markedly reduced in the combination drug–treated rats compared to the rats treated with either A. membranaceus or ligustrazine alone (P < 0.05). The neurological function, regulatory T cells, transcription factor Foxp3, transforming growth factor beta 1, interleukin 10, and interleukin 4 were markedly elevated in the rats treated with combination drugs (P < 0.05). The expression of interleukin 1 beta, interferon gamma, and interleukin 17 was reduced in the rats treated with combination drug therapy (P < 0.05).
Treatment with a combination of A. membranaceus and ligustrazine can ameliorate inflammation after thrombolysis and regulate the related cytokines by elevating the expression of endogenous regulatory T cells.
Astragalus membranaceus (Ast) and ligustrazine (Lig) have a protective effect on lower hemorrhagic transformation induced by pharmaceutical thrombolysis . The cerebral ischemia rat model was induced with autologous blood Clot injections. A combination of Ast and Lig, or a protein kinase C delta (PKCδ) inhibitor—rottlerin, or a combination of Ast, Lig, and rottlerin was administered immediately after recombinant tissue plasminogen activator injection. The cerebral infarct area, neurological deficits, cerebral hemorrhage status, neuronal damage and tight junctions’ changes in cerebral vessels, and the messenger RNA and protein levels of PKCδ, myristoylated alanine-rich C kinase substrate (Marcks), and matrix metallopeptidase 9 (MMP9) were determined after 3 h and 24 h of thrombolysis.
The ultrastructure of the neuronal damage and tight junctions was examined under a transmission electron microscope. The expression levels of PKCδ, Marcks, and MMP9 were assessed by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction . Administration of Ast and Lig not only significantly decreased neurological deficit scores, infarct volumes, and cerebral hemorrhage but also inhibited the disruption due to neuronal dysfunction and the tight junction integrity in the cerebral vessel.
Treatment with a combination of Ast and Lig effectively protected ischemia-induced microhemorrhage transformation through PKCδ/Marcks pathway suppression.
The purpose of the study was to evaluate the effect of Astragalus membranaceus extract and ligustrazine combination on ameliorating inflammation in cerebral Ischemic Diseases rats that have undergone thrombolysis. Astragalus membranaceus and ligustrazine per se, or a combination of A. membranaceus and ligustrazine was administered by intraperitoneal injection immediately after surgery and sham surgery.
After the induction of thrombolysis, the neurological function was measured and cerebral lesion volume was determined. The regulatory T cells in the spleen were measured by flow cytometry. To explore the protective effects of the combination drug on the neurological function and inflammation, the expression of transcription factor Foxp3 and cytokines, including transforming growth factor beta 1, interleukin 10, interleukin 4, interleukin 1 beta, interferon gamma, interleukin 17, in damaged brain was examined using reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay.
The cerebral lesion volume was markedly reduced in the combination drug–treated rats compared to the rats treated with either A. membranaceus or ligustrazine alone (P < 0.05). The neurological function, regulatory T cells, transcription factor Foxp3, transforming growth factor beta 1, interleukin 10, and interleukin 4 were markedly elevated in the rats treated with combination drugs (P < 0.05). The expression of interleukin 1 beta, interferon gamma, and interleukin 17 was reduced in the rats treated with combination drug therapy (P < 0.05). Treatment with a combination of A. membranaceus and ligustrazine can ameliorate inflammation after thrombolysis and regulate the related cytokines by elevating the expression of endogenous regulatory T cells.
Ethnopharmacological relevance: Hemorrhagic transformation is a frequent asymptomatic event that occurs after acute Ischemic Diseases Stroke, especially after pharmaceutical thrombolysis. However,the mechanism of hemorrhagic transformation and therapeutic s were unknown. In this study, we combine administered astragalus membranaceus and ligustrazine in rats underwent cerebral ischemia with thrombolysis; and analyzed their effects on attenuation of hemorrhagic transformation,maintaining of blood-brain barrier integrity.
Methods: A rat model of focal cerebral ischemia was induced with autologous blood Clot injection. Thrombolysis was performed via intraVenous injection of rt-PA.Astragalus membranaceus,ligustrazine or the combination of both were administered immediately after Clot injection. Cerebral infarct area,neurological deficits, blood-brain barrier integrity,and cerebral hemorrhage were determined after 3,6 and 24 hours of ischemia. Uitrastructure of blood-brain barrier was analyzed using transmission electron microscope. Tight junction protein including claudin-1,claudin-5,occludin,zonula occludens-1 expression and matrix metallopeptidase-9activation were further evaluated the role of combination drug on the protection of blood-brain barrier integrity.
Results: ischemia induced Evens blue leakage and cerebral hemorrhage were sufficiently reduced in combination treated rats compared to the astragalus membranaceus or ligustrazine alone(p0.05).The disruption of blood-brain barrier uitrastructure and neurological deficits were ameliorated after combination treatment(p0.05).It is noted that claudin-1,claudin-5,occludin and ZO-1 expression were less decreased in rats with combination treatment.In addition,MMP-9 activity was suppressed in the combination treated rats compared to the control(p0.05).
Conclusion: Combination treatment with astragalus membranaceus and ligustrazine alleviate ischemia-induced micro-hemorrhage transformation,which is through maintaining blood-brain barrier integrity.
Aucklandia costus
Ethnopharmacological relevance: Aucklandia costus Falc. a medicinal plant is native to the Himalayan region and synonymous with Saussurea costus, Saussurea lappa, and Aucklandia lappa. It has an ancient background of being used ethnopharmacologically for various body ailments. According to Ayurveda, Unani, Siddha, and Traditional Chinese Medicine, Costus roots are recommended for leukoderma, liver, kidney, blood disorders , Qi stagnation, and tridosha. Root and powder are used orally with warm water to cure gastric problems, and the paste is applied to the inflamed area to relieve pain. Root paste is applied on the skin to cure boils, blisters, and leprosy.
Aim of the study: The aim of the present review is to establish a correlation among the ethnopharmacological uses and scientific studies conducted on A. costus with chemical constituents, safety & toxicity data including future directions for its conservation with higher yield and effect.
Materials and methods: The study was conducted by studying books, research papers, and literature in history, agroforestry, phytopharmacology of Himalayan plants using international databases, publication, Red data book, and reports. The search engines: Pubmed, Scopus, Wiley Inter-science, Indian Materia Medica, Science Direct, and referred journals are referenced.
Results: The literature collected from databases, journals, websites, and books mentioned the use of costus roots in local and traditional practices. CITES included A. costus in a critically endangered category due to lack of cultural practices and overexploitation from wild. A. costus roots are known since 13th century for use in ancient Ayurvedic products but the scientific evaluation is of future research interest. A correlation of traditional uses with scientific studies has been explored to assess the effect of root powder, extract, oil and isolated constituents: Costunolids, Saussureamine B and Dehydrocostus lactone etc. in gastric ulceration and lesions; inhibition of antigen-induced degranulation, mucin production, number of immune cells, eosinophils, and expression and secretion of Th2 cytokines (IL-4 and IL-13) in asthma. The inhibition of pro-inflammatory mediators is also reported by Cynaropicrin, Alantolactone, Caryophyllene, Costic acid. Also, the sesquiterpene lactones has profound effect in inhibition of inflammatory stages and induced apoptotic cascades in cancer. Very few data on the safety and toxicity of plant parts have been noted which needs to be evaluated scientifically.
Conclusion: A. costus have been noted to have remarkable effect for gastric, hepatic, inflammatory, respiratory, cancer, skin problems but there were several errors in selection of plant material, authentification, selection of dose, assessment, selection of standard and control have been identified. Therefore, a schematic drug development and research strategy exploiting the potential of plant extract, fraction, products and probable constituents, costunolide, dehydrocostus lactone, cynaropicrin, saussureamine assuring dose-response relationship and safety may be determined under pre-clinical which may be extrapolated to clinical level. An evaluation of phytochemicals in A. costus collected from different geographical location in Himalayas may be drawn to identify and conserve the higher yielding plant.
Averrhoa bilimbi
Objective: The present study is aimed to investigate in vitro Thrombolytic activity of three Bangladeshi medicinal plants Averrhoa bilimbi (Oxalidiaceae), Clerodendrum viscosum (Verbanaceae) and Drynaria quercifolia (Polypodiaceae).
Materials and methods: Each the plant was extracted with methanol at room temperature and the concentrated methanolic extracts (MEF) were fractionated by the modified Kupchan partitioning method to render pet-ether soluble fraction (PESF), carbon tetrachloride soluble fraction (CTSF), chloroform soluble fraction (CSF) and aqueous soluble fraction (AQSF). To observe their Thrombolytic potential, a prompt and swift method was involved where streptokinase and water were used as positive and negative control, respectively.
Result: Among the three plants, AQSF and PESF of D. quercifolia with CTSF of C. viscosum exhibited highest Thrombolytic activity by Clotlysis of 34.38%, 34.27% and 28.64%, respectively. Among other extracts A. bilimbi, C. viscosun and D.quercifolia showed significant percentage (%) of Clotlysis compared to standard streptokinase (41.05%) while the negative control water revealed 3.31 % lysis of Clot .
Conclusion: From our findings it is observed that all the plants revealed remarkable Thrombolytic activity. Therefore, steps should be taken to observe in vivo Clot dissolving potential and to isolate active component(s) of these extracts.
A review on phytochemical constituents and biological assays of Averrhoa bilimbi,
Averrhoa bilimbi is a multipurpose, long-lived tropical plant commonly known as-Bilimbi, Cucumber Tree‖ belonging to family Oxalidaceae. The plant has an enormous fiscal value since most of the parts like leaves, bark, flow ers, fruits, seeds, roots or the whole plant are used as alternative medicine to treat a variety of Diseases especially diabetes.
In the present review, we tried to give the existing information on photochemical constituents, conventional medicinal uses and anti-microbial, anti-inflammatory , cyto-toxic activities, anti-oxidant activity, antifertility, and antibacterial activities and other biological activities of Averrhoa bilimbi.
The extract of various parts of Averrhoa bilimbi is medicinally used as a folk remedy for many symptoms and showed significant pharmacological activities so it is necessary to perform further investigation to isolate such pharmacological active compounds which can be used in production of novel drugs for various Diseases. Overall, this paper gives an overview on covering the biology, and various commercial and therapeutic applications.
Evaluation of fibrinolytic efficacy of Averrhoa Bilimbi linn. by using euglobulin lysis time method
Background: An impaired fibrinolytic function had been reported in subjects suffering from Venous Thrombosis . The euglobulin Clotlysis time is a test that reflects the overall fibrinolytic activity of plasma.
Objective: To evaluate the fibrinolytic efficacy of ethanolic extract of Averrhoa bilimbi Linn. leaves by using Euglobulin lysis time method.
Methods: Rats were divided into 3 groups. Each group was containing 6 rats. Group I: received vehicle (control) 0.9% saline solution; Group II: received 25 mg/kg ethanolic extract leaves of Averrhoa bilimbi Linn; Group III: received 50 mg/kg ethanolic extract leaves of Averrhoa bilimbi Linn. blood (1.8 ml) was removed with a plastic syringe containing 0.2 ml 3.8% sodium citrate solution. The time interval between the addition of thrombin and the complete lysis of the Clot s was measured. The lysis time (min) was determined.
Conclusion: We observed ethanolic extract of Averrhoa bilimbi Linn. leaves may increase the activators of the fibrinolysis. Further investigation is warranted.
In this present study, the bark extracts of Averrhoa bilimbi were subjected to the Thrombolytic activities were assessed by using human erythrocyte and the results were compared with standard streptokinase (SK). On the other hand, bark extracts of A. bilimbi revealed moderate antibacterial activity against some microorganisms used in the screening. Preliminary phytochemical investigation suggested the presence of flavonoids, saponins and alkaloids.
Azadirachta indica
Developing a new agent in the Thrombolytic field, plants are widely used for the management of Myocardial Infarction , Thromboembolic Strokes, Deep vein Thrombosis and Pulmonary Embolism . For this purpose we subjected the active compounds of to reveal its potentiality by molecular docking analysis to find out its potent compound against 1A5H which was done by Maestro v 10.1 (Schrodinger) docking analysis. Docking studies by Maestro v 10.1 (Schrodinger) showed that Gamma-Elemene of Azadirachta indica had the lowest docking score respectively against the 1A5H which are-3.001. Gamma-Elemene from Azadirachta indica detected with significant docking score which may be a potent Thrombolytic compound because the less docking score, the compound will be more potent.
Atherothrombotic Diseases such as Myocardial or cerebral Infarction are serious consequences of the thrombus formed xin blood vessels. Thrombolytic agent s are used to dissolve the already formed Clots in the blood vessels; however, these drugs have certain limitations which cause serious and sometimes fatal consequences. Herbal preparations have been used since ancient times for the treatment of several Diseases . The aim of this study was to investigate whether herbal preparations possess Thrombolytic activity or not. An in vitro Thrombolytic model was used to check the Clotlysis effect of four aqueous herbal extracts viz., O. sanctum, C. longa, A. indica, A. occidentale along with Streptokinase as a positive control and water as a negative control. The percentage (%) Clotlysis was statistically significant (p<0.0001) when compared with vehicle control.
Using an in vitro Thrombolytic model, O. sanctum, C. longa, A. indica & A. occidentale showed moderate Clotlysis activity (30.01 ± 6.168%, 32.94 ± 3.663%, 27.47 ± 6.943%, 33.79 ± 2.926% respectively) whereas standard streptokinase showed 86.2 ± 10.7 % Clotlysis effect. From our study we found that all the herbs showed reasonable % of Clotlysis.
These herbal extracts possess Thrombolytic properties that could lyse blood Clot s in vitro; however, in vivo Clot dissolving properties and active component(s) of these extracts for Clotlysis are yet to be discovered
Anti-Covid -19 potential of Azadirachta indica (Neem) leaf extract
Covid -19 is caused by infection with the “severe acute respiratory syndrome coronavirus-2″ (i.e., SARS-CoV-2). This is an enveloped virus having a positive sense, single-stranded RNA genome; like the two earlier viruses SARS-CoV and the Middle East respiratory syndrome (MERS) virus. Covid -19 is unique in that, in the severe case, it has the propensity to affect multiple organs, leading to multiple organ distress syndrome (MODS), and causing high morbidity and mortality in the extreme case. In addition, comorbidities like age, Cardiovascular Disease, diabetes and its complications, obesity, are risk factors for severe Covid -19.
It turns out that a most plausible, simple, single explanation for this propensity for MODS is the pivotal involvement of the vascular endothelium (VE). This is a consequence of the fact that the VE seamlessly connects all the entire vascular bed in the body, thus linking all the target organs (Heart, lungs, kidney, liver, brain) and systems.
Infection with SARS-CoV-2 leads to hyper-inflammation yielding uncontrolled production of a mixture of cytokines, chemokines, reactive oxygen species, nitric oxide, oxidative stress, acute phase proteins (e.g., C-reactive protein), and other pro-inflammatory substances. In the extreme case, a cytokine storm is created. Displacement of the virus bound to the VE, and/or inhibition of binding of the virus, would constitute an effective strategy for preventing Covid -19. In this regard, the acetone-water extract of the leaf of the Neem (Azadirachta indica) plant has been known to prevent the adherence of malaria parasitized red blood cells (pRBCs) to VE; prevent cytoadherence of cancer cells in metastasis; and prevent HIV from invading target T lymphocytes.
We therefore hypothesize that this Neem leaf acetone-water extract will prevent the binding of SARS-CoV-2 to the VE, and therefore be an effective therapeutic formulation against Covid -19. It is therefore advocated herein that this extract be investigated through rigorous clinical trials for this purpose. It has the advantages of being (i) readily available, and renewable in favor of the populations positioned to benefit from it; (ii) simple to prepare; and (iii) devoid of any detectable toxicity.
Antimicrobial and Thrombolytic Activities of Decoction of Azadirachta indica
The decoction of Azadirachta indica leaves were evaluated for their antimicrobial and Thrombolytic activities respectively. The antimicrobial activity was done by disk diffusion method where kanamycin (30μg/disc) was used as positive control (standard). The experiment showed highest activity against gram negative bacteria especially against E.coli and Vibrio parahaemolyticus and fungi particularly against Aspergillus niger. However, it was moderately active against gram positive bacteria.
For Thrombolytic activity, we used streptokinase as standard and normal saline and distilled water as negative control. In the test it has been observed that the decoction was moderately active for lysis of the blood Clot (27.53 ± 0.56)%. Our current studies for the first time, justified the use of decoctions of the leaves of Azadirachta indica for treating bacterial and fungal infection as well as use as thrombylitic agent in the indigenous system of medicine
Breviscapine (Erigeron Breviscapus Extract)
[Inhibitory effects of new-breviscapine on Thrombosis in vivo].
New-Breviscapine is an anti-platelet compound with some kinds of salts extracted from a Chinese herb Erigeron breviscapus. In aortic thrombus formation in rabbits, the platelet 5-HT release reaction and platelet destruction could be reduced by the compound, meanwhile aortic Thrombosis was inhibited with a clear correlation between drug dosage and its efficacy.
It was shown that new-breviscapine could inhibit the production of TXB2 and 6-keto-PGF1 alpha by platelets and endothelial cells respectively. The data suggest that new-breviscapine has a significant inhibitory effect on thrombus formation in vivo through suppression of platelet functions.
Protective effect of breviscapine in acute Pulmonary Embolism rats via regulation of MCP‐1 and IL‐13
Bre was shown to down‐regulate IL‐13 expression in the blood and further down‐regulate MCP‐1 expression, which caused alveolar macrophages (AMs) with lower cell activation efficiency.
The end result is to reduce inflammation of lung tissues, which facilitates the autologous Thrombolytic reaction and reduction in vasoconstriction in rats with PEs. Bre injections have been used >40 years, and may be recommended for the treatment of PE.
Additional clinical trials and data are warranted.
Objective: To investigate the expressions of plasminogen activator inhibitor-1 (PAI-1), activated protein C (APC) and the histology structures of the rat lung tissues in the different hypoxia time; and to investigate the effects of breviscapine to the above changes.
Methods: Eighty SD rats were randomly divided into A (control), B (hypoxia), C (hypoxia + low-dose breviscapine) and D (hypoxia + high-dose breviscopine) groups with 20 rats in each group. Each hypoxia group placed daily pressure (101 kpa, 10% O2) environment for 8 h, low-dose and high-dose breviscapine groups were given of 10 mg/kg, 40 mg/kg breviscapine by intraperitoneal injection. On the 3rd, 7th, 14th and 21st d, 5 rats were randomly taken from each group and were killed for examination. The hematoxylin and eosin stain (HE stain) was performed for observation on pathological changes in the rat lung tissues. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for detection of the mRNA levels of transforming growth factor (TGF-beta1) and Plasminogen activator inhibitor-1 (PAI-1). Western blot analysis was applied for detection of the expression of PAI-1. Besides, APC in the bronchoalveolar lavage fluid (BALF) was determined by ELISA.
Results: (1) The HE stain demonstrated that compared with A group, the degree of thickening of alveolar septal the mRNA expressions of TGF-beta1 and PA-1, and the protein expressions of PAI-1 in B group were increased (P < 0.05), and the expression of APC in the BALF was decreased (P < 0.05). And with prolonged hypoxia, the more significant of these changes were observed. Positive correlation was found between the mRNA levels of PAI-1 and TGF-beta1 (r = 0.936, P < 0.05). (2) Compared with B group, the increased thicknesses of alveolar septal in C and D groups were lightened, the mRNA expressions of TGF-beta1 and PAI-1, and the protein expression of PAI-1 were decreased (P < 0.05), and the expressions of APC in the BALF was increased (P < 0.05). With increasing dose, the expression levels of each factor gradually reduced or increased.
Conclusion: Hypoxia may cause coagulant function abnormality to increase Clotting activity and reduce fibrinolytic activity and the Anticoagulant activity, inducing alveolar septal thickening, and the mechanism of above changes may related to the TGF-beta1 signaling pathways. Breviscapine could improve hypoxia-induced hypercoagulable state that alleviate alveolar septal thickening.
therapeutic effects of Breviscapine in Cardiovascular Diseases : A Review
Breviscapine is a crude extract of several flavonoids of Erigeron breviscapus (Vant.) Hand.-Mazz., containing more than 85% of scutellarin, which has been traditionally used in China as an activating blood circulation medicine to improve cerebral blood supply.
Accumulating evidence from various in vivo and in vitro studies has shown that breviscapine exerts a broad range of Cardiovascular pharmacological effects, including vasodilation, protection against ischaemia/reperfusion (I/R), anti-inflammation, antiCoagulation, AntiThrombosis, endothelial protection, Myocardial protection, reduction of smooth muscle cell migration and proliferation, anticardiac remodeling, antiarrhythmia, blood lipid reduction, and improvement of erectile dysfunction.
In addition, several clinical studies have reported that breviscapine could be used in conjunction with Western medicine for Cardiovascular Diseases (CVDs) including Coronary Heart Disease, Myocardial Infarction, hypertension, Atrial Fibrillation, hyperlipidaemia, viral Myocarditis, chronic Heart failure, and Pulmonary Heart Disease.
However, the protective effects of breviscapine on CVDs based on experimental studies along with its underlying mechanisms have not been reviewed systematically. This paper reviewed the underlying pharmacological mechanisms in the cardioprotective effects of breviscapine and elucidated its clinical applications.
Bupleurum chinense DC. extract
Ethnopharmacological relevance: Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents Deep vein Thrombosis (DVT) through antiinflammation . However, the antiinflammatory mechanism of DHK is still unknown.
Objective: The aim of this study was to evaluate whether DHK prevented Venous Thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway.
Methods: Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. blood Coagulation , blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK.
Results: DHK remarkably prevented DVT. DHK had no effects on blood Coagulation , blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527.
Conclusion: DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.
Covid -19 has been declared a pandemic by WHO on March 11, 2020. No specific treatment and vaccine with documented safety and efficacy for the Disease have been established. Hence it is of utmost importance to identify more therapeutics such as Chinese medicine formulae to meet the urgent need. Qing Fei Pai Du Tang (QFPDT), a Chinese medicine formula consisting of 21 herbs from five classical formulae has been reported to be efficacious on Covid -19 in 10 provinces in mainland China. QFPDT could prevent the progression from mild cases and shorten the average duration of symptoms and hospital stay. It has been recommended in the 6th and 7th versions of Clinical Practice Guideline on Covid -19 in China.
The basic scientific studies, supported by network pharmacology, on the possible therapeutic targets of QFPDT and its constituent herbs including Ephedra sinica, Bupleurum chinense, Pogostemon cablin, Cinnamomum cassia, Scutellaria baicalensis were reviewed. The anti-oxidation, immuno-modulation and antiviral mechanisms through different pathways were collated.
Two clusters of actions identified were cytokine storm prevention and angiotensin converting enzyme 2 (ACE2 ) receptor binding regulation. The multi-target mechanisms of QFPDT for treating viral infection in general and Covid -19 in particular were validated. While large scale clinical studies on QFPDT are being conducted in China, one should use real world data for exploration of integrative treatment with inclusion of pharmacokinetic, pharmacodynamic and herb-drug interaction studies.
platelet anti-aggregating activities of bupleurumin from the aerial parts ofBupleurum falcatum
An aryltetralin lactone, (-)-(1S,2R,3R)-1-(3’,4’-methylenedioxyphenyl)-3-(hydroxymethyl)-6,7- dimethoxy-1, 2,3,4-tetrahydronaphthalene-2-carboxylic acid lactone, was isolated from the methanol extract of the aerial parts ofBupleurum falcatum and named bupleurumin. The structure of the compound was determined on the basis of chemical and spectroscopic methods, including two-dimensional NMR spectrometry (e.g.,1H- and13C-NMR, homo- and heteronuclear COSY, HMBC).
Bupleurumin showed an 8-fold potent inhibitory effect (IC50: 47.5 μM) compared to that of acetylsalicylic acid (ASA, IC50: 420 μM) on collagen induced platelet aggregation and comparable effects as ASA on arachidonic acid-induced platelet aggregation.
Carthamus tinctorius L.FLOWER
Anti-thrombotic effect of Carthamus tinctorius Linn extracts in rats
Purpose: To explore the effects of Carthamus tinctorius L. (CTL) extracts on Thrombosis in rats.
Methods: CTL extract was obtained in hot water (60 oC), dried in a hot air oven and then freeze-dried.The rats were divided into 6 groups: normal group, control group, reference group (aspirin 5 mg/kg) as well as groups that received 20, 40 and 80 mg/kg doses of CTL, respectively. For each group, treatment was given orally once daily for 14 days. Common carotid Artery FeCl3-induced thrombus and inferior vena cava Thrombosis occlusion time, as well as plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α(6-keto-PGF1α) were measured in rats.
Results: Compared with the control group, all doses of CTL extracts significantly and dose-dependently prolonged Thrombosis occlusion time, reduced the weight of thrombus and increased inhibition rate (p < 0.01). Plasma TXB2 concentration of all CTL extracts groups decreased dose-dependently (p < 0.05) while that of 6-keto-PGF1α was increased (p < 0.05). There was association between 6-keto- PGF1α/TXB2 and Arterial or Venous thrombus weight for all treatments, and also with occlusion time for CTL treatment but not for aspirin.
Conclusion: CTL has a significant effect on Thrombosis in rats. However, further studies are required to determine its clinical potentials.
Assessment of Clot lytic effect of Carthamus tinctorius (Golrang).
Objectives: Carthamus tinctorius, also known as Kafeshe, Golrang and Kajirein Persian, is an herb from Compositea family and its seed is traditionally called Ghortom. Flowers of Carthamus tinctorius are usually used as a food flavoring agent. Flower and oil of Carthamus tinctorius are considered as antithrombotic and anticoagulative agents in Iranian traditional medicine. In this study, the effects of different concentrations of Carthamus tinctorius extract were assessed on Clotlysis. Several in-vitro models have been developed to study Clot lytic activity of thrombolysis, but all of them have certain limitations. One of these limitations is hemolysis.
Materials and Methods: Whole blood from healthy individuals was allowed to form Clots in re-weighed sterile micro tubes; serum was removed and Clot was weighed. After lysis by seven different concentrationsof flow er extract (1.25 to 20%) fluid was removed and the remnants of the Clot were re-weighed with tubes. Percentage of Clotlysis was calculated on the basis of the weight difference of micro tubes obtained before and after Clotlysis . Also, upper fluid was used for hemolysis detecting by two methods: 1-potassium measurement 2-microscopy.
Results: The significant percentage of Clotlysis was observed when higher dosesof Carthamus tinctorius extracts were used (about 13.5%) in contrast with normal slain as a negative control (1-2%). Also no hemolysis was observed in all concentrations.
Conclusion: Carthamus tinctorius extract has Clot lytic activity in-vitro, furtheranimal studies are needed for confirming this idea.
Hemorheological disorders may play an important role in the pathogenesis and development of many Diseases . blood stasis, i.e. the decrease of blood flow velocity, indicates hemorheological abnormalities. The carthamins yellow (CY), isolated from Carthamus tinctorius L., has been extensively used as a natural food colorant. We investigated the effects of CY on a blood stasis model, which was obtained by placing rats in ice-cold water during the time interval between two injections of epinephrine. The results demonstrated that the CY significantly decreased the whole blood viscosity, plasma viscosity, and erythrocyte aggregation index, which were increased in the blood stasis model.
Hematocrit and platelet aggregation were reduced, while prothrombin time was delayed with increasing doses of CY. Therefore, CY administration might provide the additional benefit of increasing blood fluidity by lowering blood viscosity, which can be of great value in the prevention of hemorheological disorder-associated Diseases in at risk patients. Meanwhile, the mild activities of antiplatelet aggregation and antiCoagulation induced by CY should be considered, if these relatively untoward symptoms occurred when the hemorrhagic patients ate food colored by CY. However the small amounts used in food are highly unlikely to cause adverse effects.
Experiencing complications within the first two weeks after Stroke leads to a high risk of mortality and length of hospitalization. The present pilot study was intended to investigate the hypothesis that adult patients treated with safflower or not would present with fewer neurological complications following 15 days. In a randomized controlled trial, subjects diagnosed with Ischemic Diseases cerebrovascular accident (CVA) based on focal neurological findings on brain imaging who met the inclusion criteria of our study were recruited from Ghaem Hospital, Mashhad, Iran, between 2016 and 2017.
Thirty-six patients were included in the survey and randomly allocated into treatment (A) and control (B) groups. An oral syrup of safflower extract and nasal drop of safflower oil were additionally prescribed for group A. Group B only received a standard anti-Ischemic Diseases regimen. The primary outcome measure was the National Institutes of Health Stroke Scale score (NIHSS) over 15 days.
Safflower treatment led to a notably higher mean difference in the NIHSS score between the baseline score and 15-day post-treatment score in group A in comparison to group B (p < 0.001). However, adjustment for covariates (age, gender, and baseline measures) showed no significant reduction in neurological status between them (p = 0.340). There was a statistically significant difference in neurological symptom scores between the groups (p = 0.044). Based on this pilot study, adjuvant treatment with safflow er in addition to the standard anti-Ischemic Diseases regimen can be more effective than individual conventional drugs for treating Ischemic Diseases CVA among adults.
Chaenomeles sinensis (Thouin) Koehne extract
Physiological Functionalities of Hot Water Extract and Some Medicinal Materials, and Their Mixtures
The aim of this study was to investigate the physiological functionalities of Codonopsis lanceolata, Glycyrrhiza uralensis, Chaenomeles sinensis, Crataegus pinnafida, and their mixtures. We also determined their antioxidative, fibrinolytic , and lucosidase inhibitory activities. The antioxidative activities of Codonopsis lanceolata, Glycyrrhiza uralensis, Chaenomeles sinensis, and Crataegus pinnafida were 79%, 88.3%, 89.9%, and 89.3% respectively. Their fibrinolytic activities were 0.80plasmin unit/mi, 0.57 plasmin unit/mi, 0.52 plasmin unit/mi, and 0.53 plasmin unit/mi respectively. The lucosidase inhibitory activity of Codonopsis lanceolata was 25%. The 10-fold diluents of Glycyrrhiza uralensis, Chaenomeles sinensis, and Crataegus pinnafida showed lucosidase inhibitory activities of 93.6%, 65.3%, and 61.3% respectively.
In antioxidative activity tests of the medicinal plants mixtures at various ratios, the mixtures of Glycyrrhiza uralensis, Chaenomeles sinensis, and Crataegus pinnafida with Codonopsis lanceolata showed antioxidative activities of approximately 90%. In fibrinolytic activity tests mixtures(1:1) of Codonopsis lanceolata with Chaenomeles sinensis and Crataegus pinnafida exhibited increases of 23% and 24% in activity respectively.
In lucosidase inhibitory activity tests, a mixture (4:1) of Codonopsis lanceolata and 10-fold diluted Glycyrrhiza uralensis showed an inhibitory activity of 98%, a mixture (3:1) of Codonopsis lanceolata and 10-fold diluted Chaenomeles sinensis showed an inhibitory activity of 69.6%, and a mixture (1:1) of Codonopsis lanceolata and 10-fold diluted Crataegus pinnafida showed an inhibitory activity of 50.2%. In conclusion, the mixtures of Glycyrrhiza uralensis, Chaenomeles sinensis, and Crataegus pinnafida with Codonopsis lanceolata will be used as a material for the development of biofunctional foods.
Cinnamomum cassia Presl. extract
The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of Ischemic Diseases Stroke . In the study, we investigate the effects and mechanisms of the extracts of Angelica sinensis and Cinnamomum cassia (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral Artery occlusion model.
Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKKβ and IκBα, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-α, IL-1β, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased.
Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function postStroke.
Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for Ischemic Diseases Stroke treatment.
Anti-coagulant activity of plants: mini review
Medicinal plants have been used for treatment of human ailments since ancient times. Objective of this study is to document the effect of herbal drugs on Anticoagulant therapy. The material for this review was taken mostly from PubMed and the Cochrane database of systematic reviews. Some other relevant references were collected from personal database of papers on anti-coagulant properties of plants.
Literature review shows that many plants such as Thymus vulgaris, Cyamopsis tetragonoloba taub, Pulmonaria officinalis and 💥Cinnamomum cassia etc have anti-coagulant activity. This review shows that medicinal plants should be prescribed with care to patients on Anticoagulant therapy.
Citrus aurantium L. extract
Aim: Citrus fruits are well known for its medicinal and food value. Aim of this study is to investigate acetylcholinesterase ((AChE)) inhibitory activity, butyrylcholinesterase (BuChE) inhibitory activity, total phenolics, flavonoids, flavonols content and Thrombolytic activities of crude methanol extracts of 6 citrus fruits (Citrus limon, Citrus aurantifollia, Citrus bergamia, Citrus maxima, Citrus sinensis and Citrus macroptera).
Methods: The fruits were extracted by using methanol as solvent. Ellman’s colourimetric method was applied to determine both cholinesterase inhibitory activities, while folin-ciocalteau reagent (FCR) and aluminium chloride were used to quantify total phenolics, flavonoids, flavonol content of those fruits. blood Clotlysis method was applied for determining the Thrombolytic activity of those fruits.
Results: All citrus fruits contain a good amount of phenolics, flavonoids and flavonols. C. maxima found more prominent in containing phenolics and flavonols compare to other citrus fruits, with 414.06 ± 2.87 mg Gallic Acid Equivalent/gm and 12.94 ± 1.31 mg Catechin Equivalent/gm dried extract respectively. Citrus sinensis showed the highest content in flavonoids with 21.16± 1.37 mg Catechin 20 Equivalent /gm dried extract. Citrus fruits are also a quality source of cholinesterase inhibitors. All the examined citrus fruits were found capable of inhibiting both acetylcholinesterases (AChE) as well as butyrylcholinesterase (BuChE). C. bergamia was most effective in inhibiting AChE with IC50 of 27.18 μg/ml where C. macroptera was best in inhibiting BuChE (IC50 32.5 μg/ml). But none of the citrus fruits was found fit for Thrombolytic activity.
Conclusion: Citrus fruits are found the sound in inhibiting AChE and BuChE as well as containing Phenolics, flavonoids and flavonols. But they lack in their Thrombolytic activity.
An overview of Citrus aurantium used in treatment of various Diseases
Citrus aurantium (bitter orange) is a plant belonging to the family Rutaceae, The most important biologically active constituents of the C. aurantium fruits are phenethylamine alkaloids octopamine, synephrine, tyramine, N-methyltyramine and hordenine. It is rich in vitamin C, flavonoids and volatile oil.
Synephrine is a primary synthesis compound with pharmacological activities such as vasoconstriction , elevation of blood pressure and relaxation of bronchial muscle. whose fruit extracts have been used for the treatment of various Diseases such as gastrointestinal disorders, insomnia, head aches, Cardiovascular Diseases, cancer, antiseptic, anti-oxidant, antispasmodic, aromatic, astringent, carminative, digestive, sedative, stimulant, stomachic and tonic and by research novel use
is found in obesity and related risks even life threatening are continuously increasing through out world in all age groups.
Many marketed formulations claim to possess antiobesity actions, but still many herbs which have claims to this need to be investigated and their claims to be authenticated. In recent era there is a great thrust on screening of herbal extracts and formulations for antiobesity action. In this article efforts have been taken to discuss the photochemistry, constituents, ethnobotany, pharmacology safety and toxicity of citrus plant. The motto is to discuss C. aurantium here more research attention should be given on this that would increase its use in various chronic and acute Diseases.
Abstract
Ethnopharmacological relevance: Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (💥Citrus aurantium L.). DHK prevents Deep vein Thrombosis (DVT) through antiinflammation . However, the antiinflammatory mechanism of DHK is still unknown.
Objective: The aim of this study was to evaluate whether DHK prevented Venous Thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway.
Methods: Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. blood Coagulation , blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK.
Results: DHK remarkably prevented DVT. DHK had no effects on blood Coagulation , blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527.
Conclusion: DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.
Citrus assamensis
The methanol, ethanol and chlorofom leaf extracts of Satkara, Citrus assamensis (family: Rutaceae), were subjected to in vitro anti-bacterial, Thrombolytic , membrane stabilizing and in vivo anti-inflammatory and antitumor activity tests. The chloroform extract of C. assamensis showed the most important spectrum of activity against Bacillus subtilis, Bacillus cereus, Sarcina lutea among 6 gram positive and against 11 gram negative bacteria at the concentration of 1000 μg/disc, while the range of zones of inhibition were within 7-16 mm. Among the tested three extracts CHCl3 extract showed potent Thrombolytic activity and hypotonic solution induced haemolytic activity where the percentages of inhibition were found to be 35% and 55% respectively. All the extracts established significant (p<0.05) anti-inflammatory effect by regulating biphasic inflammatory process induced by carrageenan. The leaf extract dose-dependently and significantly decreases the number of EAC cell count and inhibition of cell growth in comparison to the EAC control and standard. The results obtained in the present study indicate that, C. assamensis leaf can be a potential source of anti-bacterial, Thrombolytic , membrane stabilizing, anti-inflammatory and antitumor agent s.
Phytochemical Screenings and Anti-Thrombolytic Activity of Citrus Assamenses
In this present study, the leaf extracts of Citrus assamenses were subjected to evaluate preliminary phytochemical investigation and Thrombolytic activities The Thrombolytic activity were assessed by using human blood and the results were compared with standard streptokinase (SK). The present study showed that the carbon tetra chloride soluble fraction (CSF) exhibited highest Thrombolytic activity (39.82%). However, significant Thrombolytic activity was demonstrated by the ethanol soluble fraction (ESF) of C. assamenses (35.95%), where as the positive control showed 93.29% lysis of Clot . Preliminary phytochemical investigation suggested the presence of alkaloids, tannins, reducing sugars and flavonoids.
Clerodendrum viscosum (Verbanaceae)
Objective: The present study is aimed to investigate in vitro Thrombolytic activity of three Bangladeshi medicinal plants Averrhoa bilimbi (Oxalidiaceae), Clerodendrum viscosum (Verbanaceae) and Drynaria quercifolia (Polypodiaceae).
Materials and methods: Each the plant was extracted with methanol at room temperature and the concentrated methanolic extracts (MEF) were fractionated by the modified Kupchan partitioning method to render pet-ether soluble fraction (PESF), carbon tetrachloride soluble fraction (CTSF), chloroform soluble fraction (CSF) and aqueous soluble fraction (AQSF). To observe their Thrombolytic potential, a prompt and swift method was involved where streptokinase and water were used as positive and negative control, respectively.
Result: Among the three plants, AQSF and PESF of D. quercifolia with CTSF of C. viscosum exhibited highest Thrombolytic activity by Clotlysis of 34.38%, 34.27% and 28.64%, respectively. Among other extracts A. bilimbi, C. viscosun and D.quercifolia showed significant percentage (%) of Clotlysis compared to standard streptokinase (41.05%) while the negative control water revealed 3.31 % lysis of Clot .
Conclusion: From our findings it is observed that all the plants revealed remarkable Thrombolytic activity. Therefore, steps should be taken to observe in vivo Clot dissolving potential and to isolate active component(s) of these extracts.
Roots of Clerodendrum viscosum are profoundly used throughout the world due to its ethno-medicinal properties and folkloric use since the very beginning of medicinal treatment. Due to the potential Disease preventive properties , we investigate the methanolic extracts of the roots of the plant for biological evaluation in vitro.The methanolic extract of Cl. viscosum roots was partitioned into ethyl acetate soluble fraction (ESF), petroleum ether soluble fraction (PSF), carbon tetrachloride soluble fraction (CTSF), chloroform soluble fraction (CSF) and aqueous soluble fraction (AQSF). The extracts were evaluated for their Thrombolytic , membrane stabilizing, antimicrobial and the results were compared with standard drugs; streptokinase for Thrombolytic , acetyl salicylic acid for anti-inflammatory , kanamycin for antimicrobial activities. In Thrombolytic investigation, among all partitionates, the ESF showed highest % of Clotlysis (54.47%) as compared to (69.13%) and (3.17%) exhibited by the standard streptokinase and water. In case of membrane stabilizing study, ESF also significantly inhibited the haemolysis of human erythrocyte membrane both induced by hypotonic solution (60.30 ± 0.54%) and by heat (44.21 ± 0.59%), respectively as compared to (69.01 ± 16%) and (71.90 ± 0.19%) demonstrated by acetyl salicylic acid. In antibacterial activity, it was exhibited by the extracts, was comparatively more prominent on the gram negative bacteria than the gram positive bacteria. Our study revealed that satisfactory amount of flavonoid and tannin presence showed a significant and positive correlation between bioactive compound contents with pharmacological activities of Cl. Viscosum roots.
Ethnopharmacological relevance
Cardiovascular Diseases are the major cause of mortality and morbidity, causing over 17.9 million deaths a year worldwide. Currently used therapy is often having side effects and expensive, dietary interventions and alternative medicines are required. Clerodendrum colebrookianum has been used to treat cardiac hypertension but Anticoagulant potency was not evaluated.
Aim of the study
To characterize an active Anticoagulant fraction (AAFCC) and a 30 kDa fibrin(ogen)olytic serine protease (clerofibrase) isolated from aqueous leave extract of C. colebrookianum.
Materials and methods
AAFCC/clerofibrase was subjected to extensive biochemical and pharmacological characterization including LC-MS/MS, amino acid compositional and GC-MS analyses. Interaction between clerofibrase with fibrinogen was studied by spectrofluorometric analysis. In vitro Thrombolytic , antiplatelet and cytotoxicity assay were performed. In vivo toxicity, Anticoagulant , defibrinogen and antithrombotic activities were determined on Swiss albino mice.
Results
The in vitro Anticoagulant activity of AAFCC was found to be superior to heparin and clerofibrase and comparable to Nattokinase and warfarin. The proteomics and amino acid composition analyses suggest that clerofibrase is a previously uncharacterized novel plant protease capable of degrading the -αβ chains of fibrinogen/fibrin. AAFCC/clerofibrase exerts their Anticoagulant action via fibrinogenolytic activity and partially by antiplatelet activity albeit they have no effect on thrombin and FXa inhibition . The spectrofluorometric analysis revealed the binding of clerofibrase to fibrinogen but not to thrombin and FXa. The phytochemical constituents and bioactive components of AAFCC were characterized by biochemical, and GC-MS analyses. The AAFCC and clerofibrase inhibited collagen/ADP-induced mammalian platelet aggregation , showed in vitro Thrombolytic activity, and non-cytotoxic to mammalian cells. The AAFCC showed and dose-dependent in vivo plasma defibrinogenating and Anticoagulant activities and inhibited k-carrageen-induced thrombus formation in the tails of mice.
Conclusion
The potent in vivo Anticoagulant and antithrombotic effects of AAFCC suggests its pharmacological significance as herbal Anticoagulant drug for the prevention and/or treatment of hyperfibrinogenemia- and Thrombosis associated Cardiovascular disorders .
Antihemolytic activity of Clerodendrum viscosum Vent. is mediated by its antioxidant effect.
Aims: The objective of this study was to evaluate the protective efect of polar extract of Clerodendrum viscosum vent. against in vitro hemolysis of human erythrocyte s and its asociation with the antioxidant activity of C. viscosum. Study Design: Extraction of C. viscosum dried rot, in vitro antihemolytic activity asay, lipid peroxidation asay, phytochemical analysis, estimation of polyphenols and flavonoids. Place and Duration of Study: Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka, Bangladesh, betwen January 201 and May 201.
Methodology: C. viscosum polar extract-pretreated erythrocytes were hemolysed by hypotonia and oxidizing agent, H2O2. The liberated hemoglobin was determined as a measure of hemolysis. Total reducing power and 2,2-diphenyl-1-picrylhydrazyl (DPPH)- fre radical scavenging activity of extract were compared with those of vitamin C. Antilipid peroxidation activity of C. viscosum polar extract also was determined by exposing rat brain cortex tisue to Fenton’s reagent (H2O2+FeSO4)- induced oxidative stres. Then C. viscosum extract was subjected to estimation of total polyphenols and total flavonoids folowing qualitative phytochemical analysis.
Results: C. viscosum polar extract signifcantly inhibited in vitro hemolysis. Total reducing power and DPPH-radical scavenging activity were higher than those of vitamin C. In cortical tisue homogenate, C. viscosum polar extract signifcantly reduced (~38%) the levels of lipid peroxides (LPO). Phytochemical analysis revealed the presence of substantial amount of polyphenols, flavonoids and other antioxidant chemicals in the extract.
Conclusion: Present investigation demonstrates that antihemolytic activity of C. viscosum polar extract is mediated by its antioxidant effect.
Coicis Semen extract
Background: Ischemic Diseases Stroke is a devastating Disease that causes long-term disability. However, its pathogenesis is unclear, and treatments for Ischemic Diseases Stroke are limited. Recent studies indicate that oxidative stress is involved in the pathological progression of Ischemic Diseases Stroke and that angiogenesis participates in recovery from Ischemic Diseases Stroke . Furthermore, previous studies have shown that Coicis Semen has antioxidative and anti-inflammatory effects in a variety of Diseases . In the present study, we investigated whether Coicis Semen has a protective effect against Ischemic Diseases Stroke and the mechanism of this protective effect.
Results: Coicis Semen administration significantly decreased the infarct volume and mortality and alleviated neurological deficits at 3, 7 and 14 days after MCAO. In addition, cerebral edema at 3 days postStroke was ameliorated by Coicis Semen treatment. DHE staining showed that ROS levels in the vehicle group were increased at 3 days after reperfusion and then gradually declined, but Coicis Semen treatment reduced ROS levels. The levels of GSH and SOD in the brain were increased by Coicis Semen treatment, while MDA levels were reduced. Furthermore, Coicis Semen treatment decreased the extravasation of EB dye in MCAO mouse brains and elevated expression of the tight junction proteins ZO-1 and Occludin. Double immunofluorescence staining and western blot analysis showed that the expression of angiogenesis markers and TGFβ pathway-related proteins was increased by Coicis Semen administration. Consistent with the in vivo results, cytotoxicity assays showed that Coicis Semen substantial ly promoted HUVEC survival following OGD/RX in vitro. Additionally, though LY2109761 inhibited the activation of TGFβ signaling in OGD/RX model animals, Coicis Semen cotreatment markedly reversed the downregulation of TGFβ pathway-related proteins and increased VEGF levels.
Methods: Adult male wild-type C57BL/6J mice were used to develop a middle cerebral Artery occlusion (MCAO) Stroke model. Infarct size, neurological deficits and behavior were evaluated on days 3, 7 and 14 after staining. In addition, changes in superoxide dismutase (SOD), GSH and malondialdehyde (MDA) levels were detected with a commercial kit. blood-brain barrier (BBB) permeability was assessed with Evans blue (EB) dye. Western blotting was also performed to measure the levels of tight junction proteins of the BBB. Additionally, ELISA was performed to measure the level of VEGF in the brain. The colocalization of CD31, angiogenesis markers, and Smad1/5 was assessed by double immunofluorescent staining. TGFβ pathway-related proteins were measured by western blotting. Furthermore, the cell viability of human umbilical vein endothelial cells (HUVECs) following oxygen-glucose deprivation/reoxygenation (OGD/RX) was measured by Cell Counting Kit (CCK)-8 assay.
Conclusions: Coicis Semen treatment alleviates brain damage induced by Ischemic Diseases Stroke through inhibiting oxidative stress and promoting angiogenesis by activating the TGFβ/ALK1 signaling pathway.
cordycepin
anti-inflammatory effects of cordycepin: A review
Cordycepin is the major bioactive component extracted from Cordyceps militaris. In recent years, cordycepin has received increasing attention owing to its multiple pharmacological activities. This study reviews recent researches on the anti-inflammatory effects and the related activities of cordycepin. The results from our review indicate that cordycepin exerts protective effects against inflammatory injury for many Diseases including acute lung injury (ALI), asthma, rheumatoid arthritis, Parkinson’s Disease (PD), hepatitis, atherosclerosis, and atopic dermatitis. Cordycepin regulates the NF-κB, RIP2/Caspase-1, Akt/GSK-3β/p70S6K, TGF-β/Smads, and Nrf2/HO-1 signaling pathways among others. Several studies focusing on cordycepin derivatives were reviewed and found to down metabolic velocity of cordycepin and increase its bioavailability.
Moreover, cordycepin enhanced immunity, inhibited the proliferation of viral RNA, and suppressed cytokine storms, thereby suggesting its potential to treat Covid -19 and other viral infections. From the collected and reviewed information, this article provides the theoretical basis for the clinical applications of cordycepin and discusses the path for future studies focusing on expanding the medicinal use of cordycepin. Taken together, cordycepin and its analogs show great potential as the next new class of anti-inflammatory agents.
Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2 . Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against Covid -19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach.
Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3′ hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3′-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host.
Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against Covid -19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of Covid -19.
Potent Inhibitory Activities of the Adenosine Analogue Cordycepin on SARS-CoV-2 Replication
Nucleoside analogues are among the most successful bioactive classes of druglike compounds in pharmaceutical chemistry as they are well-known for their numerous effective bioactivities in humans, especially as antiviral and anticancer agent s. Coronavirus Disease 2019 (Covid -19 ) is still untreatable, with its causing virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ), continuing to wreak havoc on the ground everywhere.
This complicated international situation urged all concerned scientists, including medicinal chemists and drug discoverers, to search for a potent anti-Covid -19 drug. Cordycepin (3′-deoxyadenosine) is a known natural adenosine analogue of fungal origin, which could also be synthetically produced. This bioactive phytochemical compound is characterized by several proven strong pharmacological actions that may effectively contribute to the comprehensive treatment of Covid -19 , with the antiviral activities being the leading ones. Some new studies predicted the possible inhibitory affinities of cordycepin against the principal SARS-CoV-2 protein targets (e.g., SARS-CoV-2 spike (S) protein, main protease (Mpro) enzyme, and RNA-dependent RNA polymerase (RdRp) enzyme) based on the computational approach. Interestingly, the current research showed, for the first time, that cordycepin is able to potently inhibit the multiplication of the new resistant strains of SARS-CoV-2 with a very minute in vitro anti-SARS-CoV-2 EC50 of about 2 μM, edging over both remdesivir and its active metabolite GS-441524.
The ideal pharmacophoric features of the cordycepin molecule render it a typical inhibitor of SARS-CoV-2 replication, with its flexible structure open for most types of derivatization in the future. Briefly, the current findings further support and suggest the repurposing possibility of cordycepin against Covid -19 and greatly encourage us to confidently and rapidly begin its preclinical/clinical evaluations for the comprehensive treatment of Covid -19.
Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent
RNA Polymerase (RdRp)
Background: SARS-CoV-2 , which emerged in Wuhan, China, is a new global threat that has killed millions of people and continues to do so. This pandemic has not only threatened human life but has also triggered economic downturns across the world. Re- searchers have made significant strides in discovering molecular insights into SARS- CoV-2 pathogenesis and developing vaccines, but there is still no successful cure for SARS-CoV-2 infected patients.
Objective: The present study has proposed a drug-repositioning pipeline for the design and discovery of an effective fungal-derived bioactive metabolite as a drug candidate against SARS-CoV-2.
Methods: Fungal derivative “Cordycepin” was selected for this study to investigate the inhibitory properties against RNA-dependent RNA polymerase (RdRp) (PDB ID: 6M71) of SARS-CoV-2 . The pharmacological profile, intermolecular interactions, binding energy, and stability of the compound were determined utilizing cheminformatic approaches. Subsequently, molecular dynamic simulation was performed to better understand the binding mechanism of cordycepin to RdRp.
Results: The pharmacological data and retrieved molecular dynamics simulations trajectories suggest excellent drug-likeliness and greater structural stability of cordycepin, while the catalytic residues (Asp760, Asp761), as well as other active site residues (Trp617, Asp618, Tyr619, Trp800, Glu811) of RdRp, showed better stability during the overall simulation span.
Conclusion: Promising results of pharmacological investigation along with molecular simulations revealed that cordycepin exhibited strong inhibitory potential against SARS-CoV-2 polymerase enzyme (RdRp). Hence, cordycepin should be highly recommended to test in a laboratory to confirm its inhibitory potential against the SARS-CoV-2 polymerase enzyme (RdRp).
Through the activation of adenosine receptors A1, A2A, A2B, and A3, adenosine plays an important role in the pathol. process of acute lung injury, such as anti-inflammatory, inhibiting cytokine storm, protecting organ damage, and repairing and remodeling tissues. cordycepin is also an activator of adenosine receptors.
It can enhance human immunity, inhibit RNA virus reproduction, anti-inflammatory, inhibit cytokine storm, protect liver, Heart, kidney, and lung fibrosis in clin. or animal models. Cordyceps and cordycepin, as a safe food supplement and(or) potential adenosine receptor agonist drug, can play a pos. role in the prevention and treatment of Covid -19 pneumonia.
At present, the novel Covid -19 pneumonia is prevalent, affecting millions of people. Here, we summarized the pharmacological basis of adenosine, adenosine receptors, adenosine agonist cordycepin (3'-deoxyadenosine), and Cordyceps product in the brain protection and amelioration of pneumonia to provide useful information to cope with the global pandemic of novel coronavirus (Covid -19 ). Adenosine, a mediator of innate immunity, is abundantly secreted by the injured lung tissues during inflammation.
Through the activation of adenosine receptors A1, A2A, A2B and A3, adenosine plays an important role in protecting against acute lung injury and brain injury. Cordycepin (3-deoxyadenosine) is an activator of adenosine receptors. It can enhance human immunity, promote anti-inflammatory processes, inhibit RNA virus reproduction, protect against brain, lung, liver, Heart, and kidney damage, and ameliorate lung-fibrosis in clinical and animal models. Cordyceps and cordycepin products could be used as a potential medicinal adenosine receptor agonist that can play a beneficial role in the amelioration of Covid -19 pneumonia and protection of brain.
Cordyceps sinensis (Berk.) Sacc extract
A novel serine protease with fibrinolytic activity named CSP was purified from the culture supernatant of the fungus Cordyceps sinensis, a kind of Chinese herbal medicine. Analysis of the purified enzyme by SDS-PAGE indicated that CSP was a single polypeptide chain with an apparent molecular weight of 31 kDa, and N-terminal sequencing revealed that the first ten amino acid residues of the enzyme were Ala-Leu-Ala-Thr-Gln-His-Gly-Ala-Pro-Trp-. When casein was used as a substrate, the proteolytic activity of CSP reached its maximum at pH 7.0 and 40 °C. The effect of chemical agent s on the enzyme activity indicated that CSP is a serine protease with a free cysteine residue near the active site.
It hydrolysed fibrinogen, fibrin and casein with a high efficiency, while hydrolysing bovine serum albumin (BSA) and human serum albumin (HSA) to a lesser extent. CSP was found to be a plasmin-like protease, but not a plasminogen activator, and it preferentially cleaved the Aα chain of fibrinogen and the α-chain of fibrin. Therefore, the extracellular protein CSP may represent a potential new therapeutic agent for the treatment of Thrombosis.
Biochemical characterization of a novel fibrinolytic enzyme from Cordyceps militaris
A fibrinolytic enzyme was produced by the medicinal mushroom, Cordyceps militaris using submerged fermentation. The enzyme was purified from culture supernatant by hydrophobic interaction, ion exchange and gel filtration chromatographies. It was purified by 36 fold, with a specific activity of 1,467.4 U/mg protein and the final yield was 5.8%. The molecular weight of the enzyme as determined by SDS-PAGE and gel filtration was 28 kDa and 24.5 kDa, respectively, and its isoelectric point (pI) was 9.0 ± 0.2. It was found to be a glycoprotein with carbohydrate content of 1.67% (w/v).
The enzyme was optimally active at 37 °C and pH 7.2. The enzyme activity was strongly inhibited by soybean trypsin inhibitor (SBTI) and aprotinin which indicated it to be a serine protease, while other inhibitors like N-α-tosyl-l-phenylalanine chloromethyl ketone (TPCK), phenyl methane sulfonyl fluoride (PMSF), pepstatin and metal chelator EDTA did not inhibit its activity. Amino acid sequences of the purified enzyme were determined partially by Q-TOF2 and they were IEDFPYQVDLR; ANCGGTVISEK; YVLTAGHCAEGYTGLNIR; TNYASVTPITADMICAGFPEGK; KDSCSGDSGGPLVTGGK; VVGIVSFGTGCAR; ANKPGVYSSVASAEIR.
Sequences of the seven peptides completely matched with those of a trypsin-like serine protease from Cordyceps militaris CM01 (accession no. EGX95217.1). The purified enzyme degraded α chains of fibrinogen first and then β and γ chains and also activated plasminogen into plasmin. It can act as an Anticoagulant and prevent Clot formation by degrading fibrinogen. Based on these studies, the purified enzyme has great potential to be developed as a natural agent for prevention and treatment of Thrombolytic Diseases.
A novel fibrinolytic enzyme from Cordyceps militaris, a Chinese traditional medicinal mushroom
A novel fibrinolytic enzyme from Cordyceps militaris was purified and partially characterized for the first time, which was designated C. militaris fibrinolytic enzyme (CMase). This extracellular enzyme from C. militaris was isolated by ammonium sulphate fraction, and purified to electrophoretic homogeneity using gel filtration chromatography. The apparent molecular mass of the purified enzyme was estimated to be 27.3 kDa by SDS-PAGE.
The optimum pH and temperature for the enzyme activity were pH 6.0 and 25 °C, respectively. In the presence of metal ions such as Mg2+ and Fe2+ ions the activity of the enzyme increased, whereas EDTA and Cu2+ ion inhibited the enzyme activity. Interestingly the N-terminal amino acid sequences of the enzyme is extremely similar to those of the trypsin proteinases from insects, and has no significant homology with those of the fibrinolytic enzyme from other medicinal mushroom. In conclusion, C. militaris produces a strong fibrinolytic enzyme CMase and may be considered as a new source for Thrombolytic agents.
A fibrinolytic Enzyme from the Medicinal Mushroom Cordyceps militaris
In this study we purified a fibrinolytic enzyme from Cordyceps militaris using a combination of ion-exchange chromatography on a DEAE Sephadex A-50 column, gel filtration chromatography on a Sephadex G-75 column, and FPLC on a HiLoad 16/60 Superdex 75 column. This purification protocol resulted in a 191.8-fold purification of the enzyme and a final yield of 12.9 %. The molecular mass of the purified enzyme was estimated to be 52 kDa by SDS-PAGE, fibrin-zymography, and gel filtration chromatography.
The first 19 amino acid residues of the N-terminal sequence were ALTTQSNV THGLATISLRQ, which is similar to the subtilisin-like serine protease PR1J from Metarhizium anisopliae var. anisopliase. This enzyme is a neutral protease with an optimal reaction pH and temperature of 7.4 and , respectively. Results for the fibrinolysis pattern showed that the enzyme rapidly hydrolyzed the fibrin -chain followed by the – chains. It also hydrolyzed the -chain, but more slowly. The A, B, and chains of fibrinogen were also cleaved very rapidly. We found that enzyme activity was inhibited by and , but enhanced by the additions of and ions.
Furthermore, fibrinolytic enzyme activity was potently inhibited by PMSF and APMSF. This enzyme exhibited a high specificity for the chymotrypsin substrate S-2586 indicating it’s a chymotrypsin-like serine protease. The data we present suggest that the fibrinolytic enzyme derived from the edible and medicinal mushroom Cordyceps militaris has fibrin binding activity, which allows for the local activation of the fibrin degradation pathway.
Integrative medicine considerations for convalescence from mild-to-moderate Covid -19 Disease
The majority of individuals infected with SARS-CoV-2 have mild-to-moderate Covid -19 Disease . Convalescence from mild-to-moderate (MtoM) Covid -19 Disease may be supported by integrative medicine strategies. Integrative Medicine (IM) is defined as healing-oriented medicine that takes account of the whole person, including all aspects of lifestyle. Integrative medicine strategies that may support recovery from MtoM Covid -19 are proposed given their clinically studied effects in related conditions. Adoption of an anti-inflammatory diet, supplementation with vitamin D, glutathione, melatonin, Cordyceps, Astragalus and garlic have potential utility.
Osteopathic manipulation, Qigong, breathing exercises and aerobic exercise may support Pulmonary recovery. Stress reduction, environmental optimization, creative expression and aromatherapy can provide healing support and minimize enduring trauma. These modalities would benefit from clinical trials in people recovering from Covid -19 infection.
Curcumae Radix extract
Background: At present, scholars believe that severe Covid -19 is related to a variety of basic Diseases , and we also observe this point using multi-omics method. The latest sequencing data of severe Covid -19 patients were combined to analyze the pathological mechanism, and pharmacological experimental research on local drugs was conducted, and a compound ingredient was found to have potential medicinal value.
Results: Here, we observed, for patients with severe Covid -19 Disease , the differential miRNA expression is mainly low but having higher expression of mRNA. These differential mRNA expressions are associated with the activation of inflammatory pathways and ultimately with hypoxia and Coagulation . Using database analysis, we found that Yi Xin Tong Mai Granule(YXTMG) might regulate Covid -19 through Toll-like receptor signaling pathway by acting on different immune targets. We found a new molecular mechanism for Covid -19 to turn the crisis around, the down-regulated miR-181a-5p mediates the up- regulation of PLAU and SERPINE1 molecules to cause Cardiovascular adverse events, and YXTMG may prevent it. At the same time, molecular docking indicated that the its various components have anti-inflammatory activity. In vitro studies, we confirmed that YXTMG had antioxidant and anti-inflammatory activities.
Conclusions: The study has supplemented the potential mechanism for the conversion of mild to critical Covid -19 Disease and screened the Chinese medicines for improving these factors, providing methodological reference for Disease pathology and drug development.
Objectives: Curcumae Radix, the medicinal part is radix, commonly called as Yujin (Chinese:), is a widely used traditional Chinese medicine for its high medicinal value and health benefits. Curcumae Radix has been used to treat conditions such as syndrome of heat Disease and unconsciousness, epilepsy and internal stagnation of phlegm, qi stagnation and blood stasis, dysmenorrhoea, jaundice, cholelithiasis caused by dampness heat of liver and gallbladder. This review aims to summarize the botany, traditional usages, processing, phytochemistry, quality control, pharmacology and toxicology of Curcumae Radix to better understand its therapeutic potential.
Key findings: So far, a variety of chemical constituents have been isolated and identified from Curcumae Radix, mainly including volatile oil and diphenylheptanes. Modern research shows that the extracts and compounds from Curcumae Radix possess wide-ranging pharmacological effects, including anti-tumour, hepatoprotective, anti-inflammatory and analgesic, AntiThrombosis, as well as effects on the nervous system and others.
Summary: Curcumae Radix holds an important position in traditional system of medicine. It is cost-effective and an important plant with curative application in contemporary medicine. However, further in-depth studies are also needed to determine the medical uses of this plant and its chemical constituents, pharmacological activity, quality control and toxicology.
The Experimental Study on Anti-thrombotic Effect of Jogantanggagambang (JGTG)
Purpose: This study was performed to evaluate anti-thrombotic effect of Jogantanggagambang extract (JGTG).
Methods: blood flow rate through the regular volume of glass tube after the blood was diluted five times with ACD solution. antithrombotic effect was calculated as a percentage of the experimental animal figure protected from the paralysis of hind legs or death of the mouse that was caused from the administration of platelet aggregation regent.
Results: 1. JGTG inhibited the platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid as compared with the control group. 2. JGTG inhibited Pulmonary Embolism induced by collagen and epinephrine (inhibitory rate is 37.5%). 3. JGTG increased platelet number and fibrinogen amount significantly and also JGTG shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. 4. JGTG increased blood flow rate significantly as compared with the control group in vivo.
Conclusion: These results suggest that JGTG can be used for treating various female Diseases caused by Thrombosis.
Cyathula officinatis Kuan root extract
Background: Cyathula officinalis Kuan is widely used in the clinics for the treatment of blood stasis in China.
Objective: To evaluate the improving blood rheology and anti-inflammatory properties of C. officinalis Kuan extract (CO) and its active fraction (ACO) on acute blood stasis model Wistar rats and characterize the correlative constituents.
Materials and Methods: CO at 0.26, 0.53, and 1.04 g/kg and ACO at 0.38, 0.75, and 1.5 g/kg were administered to acute blood stasis model Wistar rats for 3 days. Whole blood viscosity, plasma viscosity, and the levels of interleukin-6 (IL-6), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) in the plasma were measured. HPLC-QTOF/MS/MS method was used to identify the major constituents of ACO; the properties of two representative components (cyasterone and chikusetsusaponin IV) from ACO on thrombin -induced human umbilical vein endothelial cells damage model were also assessed by the levels of thromboxane A2 (TXA2), endothelin (ET), malondialdehyde (MDA), COX-2, endothelial nitric oxide synthase (eNOS), and superoxide dismutase (SOD).
Results: CO and ACO significantly reduced whole blood viscosity, plasma viscosity, and levels of IL-6, NO, TNF-α, and COX-2 in vivo. Forty compounds were identified from ACO, mainly as phytoecdysteroids and saponins. Cyasterone and chikusetsusaponin IV could significantly inhibit levels of TXA2, ET, MDA, and COX-2 and promote the activities of eNOS and SOD in vitro.
Conclusion: CO and ACO possessed significant improving blood rheology and anti-inflammatory effects on acute blood stasis model rats and the representative components Cyasterone and chikusetsusaponin IV showed significant anti-inflammatory, antioxidant, and Anticoagulant effects in vitro.
Cyathulae Radix extract
Xuefu Zhuyu Tang (XFZY), a famous formula in traditional Chinese medicine, has been demonstrated to show good therapeutic effects on Diseases caused by blood stasis syndrome. Two of its eleven herbs, Radix Platycodonis and Radix Cyathulae, have been considered as Shi ingredients in the hierarchy of traditional formula compatibility and proven possessing synergistic properties that strengthen the formula’s potency of activating blood circulation and resolving blood stagnation.
However, its mechanism is still not clearly elucidated. In our previous study, we observed their effects on paeoniflorin pharmacokinetics of XFZY in rats. In this study, we continued by detecting and comparing their effect on the tissue distribution of paeoniflorin after oral administration of XFZY and its three variants (XFZY without Radix Platycodonis or/and Radix Cyathulae) in blood-stasis mice via HPLC assay.
The results indicated that combining usage of Radix Platycodonis and Radix Cyathula increased the distribution of paeoniflorin in the lung and kidney and introduced the paeoniflorin into the liver, spleen and Heart. It might explain their synergistic properties that strengthen the formula’s effect of invigorating blood and dissolving stasis and provide experimental evidence to understand the pharmacological effects of Shi herbs in the hierarchy of traditional formula compatibility.
Virtual Screening of Potential AEC2 Inhibitors for Covid -19 from Traditional Chinese Medicine
Background: Angiotensin-converting enzyme 2 (ACE2 ), a negative regulator of the renin-angiotensin system and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor, plays an important role in viral genome replication and immune response. ACE2 has been proposed as a potential therapeutic target. Traditional Chinese medicine (TCM) could be considered as a promising complementary therapeutic option in the management of Covid -19 . However, the active components and action mechanisms that account for its therapeuti effects remain controversial.
Methods: ACE2 was employed as a target related to Covid -19 to explore the active ingredients from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. And the PharmMapper database and TCMSP database were used to predict the targets of the compounds. Moreover, the potential therapeutic targets of Covid -19 were acquired by intersection among genes differentially expressed in Covid -19 patients, genes screened from
Objective: To explore the action mechanism of five Chinese medicines targeting ACE2 for the treatment of Covid -19 .
Methods: Chinese medicines with human angiotensin converting enzyme II (ACE2 ) targeting activity were screened through the traditional Chinese medicine (TCM) system pharmacology database and analysis platform (TCMSP), and the TCMSP platform was further utilized to identify the active ingredients of Chinese medicines and their corresponding drug targets. Then, the protein interaction of the above protein targets was analyzed by STRING online database and the relevant data were downloaded. Next, the core sub-network modules in the PPI network system were screened through the MCODE plug-in in CytoScape 3.2.1 software. The functional enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out, using online enrichment analysis software DAVID v6.8, to predict the pharmacological mechanism of the above five Chinese medicines, and to verify and explore the feasibility of compatibility and clinical application of related herb-pair or formula under the theoretical system of TCM.
Results: Five Chinese medicines with potential therapeutic effects on ACE2 were selected through the TCMSP platform, namely Bupleuri Radix, Puerariae Lobatae Radix, Puerariae Lobatae Flos, Cyathulae Radix, and Hemerocallis Radix, which contained 42 active ingredients and 240 drug targets. The results of GO biological function enrichment analysis showed that the above five Chinese medicines could affect the biological processes such as inflammatory response, cell apoptosis and proliferation and etc. The results of KEGG pathway enrichment analysis showed that the pharmacological mechanisms of these Chinese medicines were closely related to PI3K-Akt pathway, TNF pathway, FoxO pathway, MAPK pathway, and so on. In TCM theory, Bupleuri Radix and Puerariae Lobatae Radix is a classic herb-pair for the treatment of infectious and febrile Diseases . Chaige Jieji Decoction is widely used in febrile Diseases in ancient and modern clinics, and has achieved good clinical effects . The main febrile Disease treated by this herb-pair is the triple-yang combination of Diseases in the syndrome differentiation of the six meridians, which is in line with the syndrome differentiation of TCM in patients with SARS-CoV-2 infection. It can be used with Cyathulae Radix and Hemerocallis Radix in addition and subtraction.
Conclusion: The identified five Chinese medicines have multi-target, multi-function and multi-pathway pharmacological effects on the treatment of Covid -19 . According to the theoretical analysis of TCM and previous clinical experience, it is suggested that Chaige Jieji Decoction or Bupleuri Radix and Puerariae Lobatae Radix herb-pair can be used to treat Covid -19 .
The outbreak of Covid -19 raises an urgent need for the therapeutic s to contain the emerging pandemic. However, no effective treatment has been found for SARS-CoV-2 infection to date. Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP).
Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2 , which was validated by surface plasmon resonance (SPR) assay. Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor. Notably, quercetin could also bind to the RBD domain of S-protein, suggesting not only a receptor blocking, but also a virus neutralizing effect of quercetin on SARS-CoV-2.
The results from network pharmacology and bioinformatics analysis support a view that quercetin is involved in host immunomodulation, which further renders it a promising candidate against Covid -19. Moreover, given that puerarin is already an existing drug, results from this study not only provide insight into its action mechanism, but also propose a prompt application of it on Covid -19 patients for assessing its clinical feasibility.
Dimocarpus longan Lour. extract
The biosynthesis of nanoparticles has been proposed as a cost-effective and environmentally friendly alternative to chemical and physical methods. In the present study, the synthesis of silver oxide nanoparticles has been achieved using Dimocarpus longan fruit. The fruit extract can act as both the reducing agent and stabilizing agent. The synthesized silver oxide nanoparticles were characterized using UV-visible spectrometer the peak observed at 460 nm, FT-IR spectrum implies that polyphenolic compounds were responsible for the formation of silver oxide nanoparticles, XRD analysis, Scanning Electron microscope (SEM) shows poly dispersed nanoparticles and EDAX spectrum shows sharp peak at 3 KeV.
The particle size range was found to be 30 to 123 nm and the stability calculated by Zeta potential was −25 mV. The prepared silver oxide nanoparticles were investigated for their catalytic activity on the reduction of p-nitrophenol(4-NP) to p-aminophenol(4-AP). The fruit extract of silver oxide nanoparticles was biologically active and exhibit antifungal activity.
The antioxidant potential of silver oxide nanoparticles were investigated by DPPH assay and the IC50 value was found to be 60 μgml−1. The anticancer activity of silver oxide nanoparticles was determined using MTT assay against MCF-7 breast cancer cells.
Preliminary Observation on the fibrinolytic Activity of Dimocarpus longan Seed
Dragon’s blood from Dracaena cochinchinensis (Lour.) S.C. Chen
Ethnopharmacological relevance: Dragon’s blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragon’s blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments.
Materials and methods: A rat/mouse Thrombosis and blood stasis model was developed for this study, and EA and PB effects on Thrombosis, platelet functions and blood Coagulation activities were analyzed.
Results: It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on Thrombosis (p < 0.05), platelet aggregation function (p < 0.01) and anti-Coagulation activity (p < 0.05–0.01).
Conclusions: The results obtained here showed that EA fraction from Dragon’s blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and antiCoagulation activity.
Comparison of the chemical profiles and anti-platelet aggregation effects of two “Dragon’s blood” drugs used in traditional Chinese medicine
Ethnopharmacological relevance: “Dragon’s blood” has been used as a medicine since ancient times by many cultures. In traditional Chinese medicine, the resin obtained from Daemonorops draco (RDD) and the resin from Dracaena cochinchinensis (RDC) are equally prescribed as “Dragon’s blood” for facilitating blood circulation.
Aim of the study: To verify the traditional efficacy and elucidate the mechanism, the present study compared the chemical profiles and the pharmacological effects of two species of “Dragon’s blood” mainly used in China.
Materials and methods: A UPLC-MS fingerprinting method was developed to compare the chemical profiles of the two medicines. The anti-platelet aggregation effects of the two medicines induced by arachidonic acid (AA) were investigated.
Results: The chemical profiles of these two species of “Dragon’s blood” were significantly different. The characteristic constituents were found to be: flavanes in RDD and stilbenes in RDC. In the in vivo platelet inhibition test, performed with the dose of 200 mg/kg on rats, the peak inhibitory effects of RDD and RDC were 35.8% and 27.6%, respectively, compared with the control group. With the in vitro concentrations of 0.2, 0.4 and 0.8 mg/ml, RDD exerted significant inhibition of aggregation by 18.7%, 20.0%, and 61.6%, respectively, and RDC exerted significant inhibition of aggregation by 13.3%, 20.2%, and 31.6%, respectively.
Conclusion: The fingerprinting method used here is suitable for distinguishing them. All pharmacological tests indicated that RDD was more potent than RDC against platelet aggregation.
Drynaria quercifolia (Polypodiaceae)
Background: Drynaria quercifolia L. (Family- Polypodiaceae) is a fern grows in Bangladesh used in traditional healing by the Garo tribe of Mymensingh district. In the current study, rhizomes and fertile foliage fronds of this plant have been investigated comprehensively to assess their in vitro membrane stabilizing, Thrombolytic and antioxidant properties .
Methods: Rhizomes and fertile foliage fronds of D. quercifolia were collected, dried, powdered and extracted with methanol. Later on, crude methanol extracts of the plant parts were fractionated into petroleum ether, carbon tetrachloride, chloroform and aqueous soluble fractions. The extractives were then subjected to membrane stabilizing, Thrombolytic and antioxidant assays.
Results: In membrane stabilizing assay, crude methanol extracts of rhizomes and fertile foliage fronds and their petroleum ether fractions were found to be very effective for stabilizing erythrocyte membrane in hypotonic solution. In case of Thrombolytic study, crude methanol extract of rhizomes and its aqueous fraction exhibited noticeable Clotlysis . However, in antioxidant assays, crude methanol extracts of the tested plant parts and their aqueous fractions exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide and 2, 2’-azinobis (3-ethylbenzothiazoline sulphonic acid) (ABTS) radical scavenging activity. Besides, these extractives also displayed substantial ferric reducing potential in ferric reducing antioxidant power (FRAP) assay. Crude methanol extracts of the plant parts and their aqueous fractions were also found rich in phenolics.
Conclusion: This study demonstrates the medicinal potentials of D. quercifolia and justifies the local uses of it by the Garo tribal people of Bangladesh for multiple Disease management.
Drynaria quercifolia is a medicinal pteridophyte which have been treated by the administration of plant parts based on traditional and folk uses since ancient times. Considerable utilization and progress have been achieved regarding its biological activities. Various phytoconstituents like 3,4-dihydroxybenzoic acid, friedelin, epifriedelinol, coumarins β-amyrin, β-sitosterol and β-sitosterol 3-β-D-glucopyranoside has been isolated from the plant and these bioactive compounds responsible for its antidermatophytic, antimicrobial, antifertility, anti-lipidperoxidative, antiulcer, antipyretic, anti-arthritis, anti-urolithiatic, Pesticidal and Pest Repellency, Thrombolytic and various other activities.
Considering the ethnomedicinal significance of this parasitic fern, an attempt has been made for the first time to review to provide up to date clinical reports on the plant and to document the available phytochemical constituents through data base searches (PubMed, Google scholar, Scopus).
EGb 761 from Ginkgo biloba extract
The antiplatelet and antithrombotic effects of the oral combination treatment of ticlopidine and Ginkgo biloba extract (EGb 761) were studied in normal and Thrombosis -induced rats. The ex vivo inhibitory effect on ADP-induced platelet aggregation of a small dose of ticlopidine (50 mg/kg/day) in combination with EGb 761 (40 mg/kg/day) was comparable to a larger dose of only ticlopidine (200 mg/kg/day). Bleeding time was also prolonged by 150%. thrombus weight was also consistently decreased by a combination of ticlopidine and EGb 761 in an arterio-Venous shunt model at two doses of ticlopidine (50 mg/kg) plus EGb 761 (20 mg/kg) and ticlopidine (50 mg/kg) plus EGb 761 (40 mg/kg). A combinatory treatment in acute Thrombosis model in mice also showed a higher recovery than a single treatment.
1. An extract of Ginkgo biloba (EGb 761) has been reported to alleviate cerebrovascular problems. In the present study, we investigated the antithrombotic effects of EGb 761 in cerebral blood vessels of Stroke -prone spontaneously hypertensive rats (SHRSP/Izm).
2. In the present study, EGb 761 was administered orally to SHRSP/Izm at 60 and 120 mg/kg each day for 3 weeks from the age of 7 weeks. The age-related increase in blood pressure observed in SHRSP was suppressed significantly by EGb 761 at both doses 3 weeks after treatment.
3. Thrombotic potential was assessed in vivo using a He-Ne laser-induced Thrombosis model and was significantly suppressed by EGb 761.
4. The anti-oxidant effects of EGb 761 were determined by measurement of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG). At 120 mg/kg, EGb 761 decreased 8-OHdG significantly compared with control animals.
5. Urinary nitrite/nitrate, nitric oxide (NO) metabolites, were increased significantly after administration of EGb 761. Expression of endothelial NO synthase (eNOS) mRNA was measured using a real-time quantitative reverse transcription–polymerase chain reaction method. The expression of eNOS mRNA in the EGb 761 group (120 mg/kg) was significantly higher than in the control group.
6. The results indicate that EGb 761 decreases blood pressure and mediates strong antithrombotic and anti-oxidant effects in SHRSP. These pharmacological activities may contribute to the beneficial properties of EGb 761 observed in clinical practice.
fibrinolytic effects of Ginkgo biloba extract
A multitude of factors are involved in regulating the blood Coagulation homeostatic processes in the body, which may ultimately lead to thromboemboli and Thrombosis. The resolution of blood clots after healing is as important as Clot formation at the site of a vascular lesion. This is accomplished by fibrinolytic drugs such as streptokinase (SK) and urokinase.
It must be noted that administration of SK may be accompanied by the lysis of blood Clot s in unwanted sites, and complications such as general lytic conditions, severe hemorrhaging, reduced serum fibrinogen and allergies can occur. Anti-SK antibodies neutralize the effects of SK. Studies on natural compounds and medicinal herbs with fewer side effects have been ongoing. In the present study, the fibrinolytic effect of Ginkgo biloba, an herb grown in Iran, was investigated.
A polyphenolic method was used to obtain Ginkgo extract from its leaves. The fibrinolytic effects of SK (positive control) were compared with those of Ginkgo extract using a fluorometry method.
In producing a labelled Clot, fibrinogen was labelled with the fluorescent agent fluorescein isothiocyanate and precipitated in the presence of Ca2+. SK (100 U/mL to 1000 U/mL) and Ginkgo extract were added to labelled fibrin in a plasma environment at dilutions of 1, 1:10, 1:100 and 1:1000 (volume/volume). The fluorescence of the solution was measured between 15 min and 60 min later.
A linear relationship was observed between the fluorescence measured and SK concentrations ranging from 300 U/mL to 700 U/mL. Ginkgo extract displayed a remarkable effect in resolving the Clot. As Ginkgo extract remained in the environment, fluorescence increased notably, showing a time-dependent relationship.
Overall, the results indicate that the effects of Ginkgo extract on the fibrinolytic system are similar to those of SK; hence, this herbal extract can be used as a complement to or a substitute for SK. Additionally, it is proposed that the effects of the active ingredients of Ginkgo extract should be studied in animals. Further studies are warranted for evaluating the possible side effects and toxicity of Ginkgo extract in human subjects.
Inhibitory effect of Ginkgo biloba extract on human platelet aggregation
The effect of pure flavonoids and Gingko biloba extract (GBE) on human platelet aggregation was investigated. Most of the flavonoids and vitamin E did not affect platelet aggregation in platelet-rich plasma (PRP); however some of these flavonoids inhibited platelet aggregation in gel-filtered platelets (GFP). GBE inhibited both ADP- and collagen-induced platelet aggregation in PRP, GFP and in whole blood in a dose-dependent manner. GBE at very low concentrations inhibited whole blood aggregation induced by ADP compared with those used for PRP or GFP. Flavonoids and GBE decreased the production of TxA 2 induced by collagen and ADP in PRP.
owever, no correlation was observed between the inhibition of platelet aggregation and the decrease of TxA 2 synthesis. GBE and flavonoids did not affect platelet membrane fluidity. However, the incubation of PRP with GBE increased cAMP levels in platelets, which is known to inhibit platelet activation by lowering intracellular Ca2+ levels. GBE is a mixture of many compounds, including flavonoids and gingkoglides, which affect metabolism of cAMP, TxA2 and Ca2+ in platelets. It is effective in the inhibition of platelet aggregation, both in PRP and whole blood, and thus may be potentially used as an effective oral anti-platelet therapeutic agent.
effects of Ginkgo biloba on blood Coagulation Parameters
A systematic literature review was conducted to investigate the effects of Ginkgo biloba preparations on blood Coagulation parameters. Systematic literature searches were carried out using MEDLINE (via PubMed), EMBASE, AMED, CINAHL®, the Cochrane Library and PsycINFO to identify randomised, double-blind, clinical trials of G. biloba mono-preparations assessing at least one blood Coagulation parameter as either a primary or a supplementary outcome measure. Five manufacturers of G. biloba preprations were asked to contribute any unpublished material. Data were validated and extracted independently by two reviewers according to pre-specified criteria.
Eight trials were included, of which two included healthy subjects, four included patients with various conditions and two included participants taking concomitant Anticoagulant medication, one with acetylsalicylic acid (ASA; aspirin) and one with warfarin. Overall results do not provide evidence that G. biloba does affect blood Coagulation parameters in a clinically relevant manner. Out of many parameters assessed, four Coagulation parameters from three studies were significantly different in the treatment group compared with the control. One study comparing the treatments of ASA and G. biloba with ASA alone confirmed that the two treatments were equivalent with regards to all but three Coagulation parameters.
Available evidence does not demonstrate that extract of G. biloba causes significant changes in blood Coagulation parameters. A limited number of studies on concomitant use of G. biloba with ASA or warfarin also do not suggest that G. biloba has an additive effect to the clinical effects of these two drugs. Currently available evidence is limited and, therefore, further studies are needed to assess effects of G. biloba on a variety of blood Coagulation parameters.
Evodia rutaecarpa (Juss.) Benth extract
In this study, platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intraVenous ly with fluorescein sodium. Rutaecarpine (200 µg/g) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules when it was intravenously injected. Rutaecarpine (200 µg/g) prolonged occlusion time by approximately 1·5-fold (control 127 ± 29 vs. taecarpine 188 ± 23 s). Furthermore, aspirin (250 µg/g) also showed a similar prolongation of the occlusion time in this experiment. On a molar basis, rutaecarpine was approximately twofold more potent than aspirin at prolonging the occlusion time.
Furthermore, rutaecarpine was also effective in reducing the mortality of ADP-induced acute Pulmonary thromboEmbolism in mice when administered intravenously at doses of 25 and 50 µg/g. Intravenous injection of rutaecarpine (50 µg/g) significantly prolonged the bleeding time by approximately 1·5-fold compared with normal saline in the severed mesenteric arteries of rats. Continuous infusion of rutaecarpine (5 µg/g/min) also significantly increased the bleeding time 1·5-fold, and the bleeding time returned to baseline within 60 min after cessation of rutaecarpine infusion.
These results suggest that rutaecarpine has an effective anti-platelet effect in vivo and that it may be a potential therapeutic agent for Arterial Thrombosis, but it must be assessed further for toxicity.
The role of activated platelet s in acute and chronic Cardiovascular Diseases (CVDs) is well established. Therefore, antiplatelet drugs significantly reduce the risk of severe CVDs. Evodia rutaecarpa (Wu-Chu-Yu) is a well-known Chinese medicine, and rutaecarpine (Rut) is a main bioactive component with substantial beneficial properties including vasodilation . To address a research gap, we investigated the inhibitory mechanisms of Rut in washed human platelets and experimental mice. At low concentrations (1–5 μM), Rut strongly inhibited collagen-induced platelet aggregation, whereas it exerted only a slight or no effect on platelets stimulated with other agonists (e.g., thrombin ).
Rut markedly inhibited P-selectin expression; adenosine triphosphate release; [Ca2+]i mobilization; hydroxyl radical formation; and phospholipase C (PLC)γ2/protein kinase C (PKC), mitogen-activated protein kinase, and phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β) phosphorylation stimulated by collagen. SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor) did not reverse Rut-mediated antiplatelet aggregation. Rut was not directly responding to vasodilator-stimulated phosphoprotein phosphorylation.
Rut significantly increased the occlusion time of fluorescence irradiated thrombotic platelet plug formation. The findings demonstrated that Rut exerts a strong effect against platelet activation through the PLCγ2/PKC and PI3K/Akt/GSK3β pathways. Thus, Rut can be a potential therapeutic agent for Thromboembolic disorders.
Effect of Evodiamine on Collagen-Induced platelet activation and Thrombosis
Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, Cardiovascular Disease, cancer, and other chronic Diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and Thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen.
Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLCγ2 activation pathway in platelet s. According to in vivo studies, Evo significantly prolonged the mesenteric thrombo embolism induced by ferric chloride and had no discernible effect on the Coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.
Evodia rutaecarpa (Chinese name: Wu-Chu-Yu) is a well-known traditional Chinese medicine and has long been used in Chinese medical practice. Rutaecarpine is an indolopyridoquinazolinone alkaloid isolated from E. rutaecarpa and related herbs, which has been shown to have Cardiovascular biological effects, such as inotropic and chronotropic, vasorelaxant, antiplatelet aggregation, and anti-inflammatory effects.
Furthermore, it has been reported that rutaecarpine has beneficial effects on some Cardiovascular Diseases. This review was undertaken to summarize data on the Cardiovascular pharmacological actions of rutaecarpine published over the recent years, aiming to provide more evidence supporting its use in the treatment of Cardiovascular Diseases. This review also reveals some interesting and unique pharmacological properties, which may explain its vascular and platelet effects.
Rutaecarpine: A promising Cardiovascular protective alkaloid from Evodia rutaecarpa (Wu Zhu Yu)
Rutaecarpine is a bioactive alkaloid isolated from Evodia rutaecarpa (Wu Zhu Yu, Family: Rutaceae), a versatile medicinal herb which is clinically used to treat headache, abdominal pain, postpartum hemorrhage, dysentery, and amenorrhea in China. As one of the most representative indolopyridoquinazoline alkaloids of Evodia rutaecarpa, rutaecarpine has broad pharmacological actions in treating various Cardiovascular, cerebrovascular, and metabolic diseases.
The Cardiovascular actions of rutaecarpine have aroused intense research interest due to its purported inotropic and chronotropic, vasodilatory, anti-platelet activation, anti-oxidant, anti-inflammatory, and lipid-lowering effects. Biochemical and pharmacological studies have illustrated the molecular targets of rutaecarpine, such as TRPV1, CGRP, AMPK, ABCA1, and β1-AR. Furthermore, several rutaecarpine derivatives (such as bromorutaecarpine and fluororutaecarpine) have been shown to possess cardioprotective and vasculoprotective effects with improved safety profile.
Hereby, we provide a systematic overview of pharmacological actions, toxicological effects, and molecular targets of rutaecarpine in Cardiovascular Disease prevention/treatment, aiming to exploit the therapeutic potential of rutaecarpine and its derivatives in treating Cardiovascular Diseases.
Ganoderma lucidum
fibrinolytic and antithrombotic protease from Ganoderma lucidum
A putative metalloprotease was purified from mycelium of Ganoderma lucidum. The enzyme was purified by anion exchange, chromatofocusing, and gel filtration chromatography. The Mr was determined to be 52 000 by SDS-PAGE and 100 000 by gel filtration on a Sephadex G-150 column, indicating that it is a dimer. The enzyme was inhibited by EDTA, 1,10-phenanthroline, and phosphoamidon. The presence of Zn2+ was detected by ICP mass spectral analysis as 1.1 mol of Zn2+ per mol of protease.
This protease hydrolyzed Aα and Bβ chains of human fibrinogen, but did not cleave thrombin, albumin, hemoglobin, and immunoglobulin under the same condition. It also showed an Anticoagulant activity in human plasma. The enzyme delayed the activated partial thromboplastin time and thrombin time, but not the Clot ting induced by reptilase, indicating Ganoderma protease is specific to thrombin. Ganoderma protease behaved as a competitive inhibitor of thrombin-catalyzed fibrin formation, but no inhibition of thrombin was found with a small synthetic peptide. These observations indicate that Ganoderma protease could bind thrombin at an anion binding exosite distinct from the active site and cause the delay of Clot ting time induced by thrombin.
antithrombotic activity of a protease purified from a medicinal mushroom, Ganoderma lucidum, has been evaluated platelet aggregation in vitro and Pulmonary Thrombosis in vivo. The purified protease exhibited concentration dependent inhibitory effects on platelet aggregation induced by ADP (adenosine diphosphate), with an IC50 value of 2.4 mg/mL. The purified protease protected mice against thrombotic death or paralysis induced by collagen and epinephrine in a dose dependent manner when administered orally. It produced a significant inhibition of thrombotic death or paralysis at 60μg/kg body weight, while aspirin produced a significant inhibition of Thrombosis at 10-20 mg/kg body weight.
The purified protease also has showed fibrinolytic activity and alters Coagulation parameters such as activated partial thromboplastin time (APTT), and thrombin time (TT) in rat platelet. These results suggested that the antithrombotic activity of Ganoderma lucidum protease might be due to antiplatelet activity rather than antiCoagulation activity.
In vitro Doses and Incubations Dependent Thrombolytic Potential Study of Edible Mushrooms Pleurotus ostreatus, Ganoderma lucidum and Lentinula edodes Available in Bangladesh
Aims: The study was carried out to investigate the Thrombolytic potential of methanolic extracts of edible mushrooms.
Study Design: Experimental study. Place and Duration of Study: Department of Biochemistry, Primeasia University, August 2014 to December 2014
Methodology: An in vitro Thrombolytic model was used to check the Thrombolytic effect of Pleurotus ostreatus, Ganoderma lucidum and Lentinula edodes along with Streptokinase as a positive control and water as a negative control. In this study two concentrations of the extracts i.e. 400μg/ml and 800 μg/ml were tested at three time intervals, 24 hrs, 48 hrs and 72 hrs duration of incubation at 37ºC for observing maximum Clotlysis.
Results: At 400 μg/ml dose, Pleurotus ostreatus showed highest Clotlysis activity in 72 hrs of incubation, 18.62% while Ganoderma lucidum, and Lentinula edodes showed 17.01% and 9.02% in the same incubation. Similarly, at 800 μg/ml dose, the Thrombolytic activities were 63.35%,
Gastrodiae Rhizoma extract
The effects of acidic polysaccharides purified from Gastrodia rhizome on blood pressure and serum lipid levels in spontaneously hypertensive rats (SHR) fed a high-fat diet were investigated. Acidic polysaccharides were purified from crude polysaccharides by DEAE-Sepharose CL-6B. Thirty-six male SHR were randomly divided into three groups: Gastrodia rhizome crude polysaccharide (A), acidic polysaccharide (B) groups, and a control group (C). A 5-week oral administration of all treatment groups was performed daily in 3- to 8-week-old SHRs with a dose of 6 mg/kg of body weight/day.
After 5 weeks of treatment, total cholesterol in the acidic polysaccharide group, at 69.7 ± 10.6 mg/dL, was lower than in the crude polysaccharide group (75.0 ± 6.0 mg/dL) and the control group (89.2 ± 7.4 mg/dL). In addition, triglyceride and low-density lipoprotein cholesterol levels in the acidic polysaccharide group were lower than in the crude polysaccharide and control groups. The atherogenic index of the acidic polysaccharide group was 46.3% lower than in the control group.
Initial blood pressure after the initial three weeks on the high-fat diet averaged 195.9 ± 3.3 mmHg among all rats. Compared with the initial blood pressure, the final blood pressure in the control group was increased by 22.8 mmHg, whereas it decreased in the acidic polysaccharide group by 14.9 mmHg. These results indicate that acidic polysaccharides from Gastrodia rhizome reduce hypertension and improve serum lipid levels.
Testosterone deficiency deteriorates glucose and lipid metabolism with reducing muscle mass. We investigated whether the consumption of water extracts of Gastrodia elata Blume rhizome (GEB) rich in gastrodin would reduce the symptoms of testosterone deficiency and improve blood flow in orchidectomized (ORX) rats. ORX rats were given high-fat diets supplemented with either 1% cellulose (ORX-control), 0.3% GEB (GEB-L), or 1% GEB (GEB-H) for 8 weeks.
Sham-operated rats were fed the same diet as OVX-control rats (normal-control). ORX-control rats had reduced serum testosterone levels by one-fifth, compared to normal-control rats. ORX-control rats exhibited decreased lean body mass, attenuated blood flow, and impaired cholesterol metabolism and glucose control due to decreased insulin secretory response. GEB increased serum insulin levels dose-dependently and GEB-H mostly enhanced dyslipidemia in ORX rats. GEB completely normalized Arterial Thrombosis time and blood flow in ORX rats.
Interestingly, ORX-control rats showed attenuated hepatic insulin signaling but greater AMPK and CREB activities, which reduced triglyceride accumulation, compared to normal-control. GEB-H improved hepatic insulin signaling but maintained the AMPK and CREB activities in ORX rats. In conclusions, GEB ameliorated the impairment of cholesterol and glucose metabolism and blood flow in ORX rats. GEB may be a potential preventive measure for reducing the risk of Cardiovascular Diseases associated with testosterone deficiency.
Haliotis diversicolor Reeve extract
Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin.
Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying Clot ting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients.
Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic.
To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until Clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low.
Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.
To screen the more promising antithrombotic abalone extracts, the in vitro antithrombotic activity of 6 abalone (Haliotis Discus Hannai Ino) extracts was examined in this study. Results of in vitro studies indicated that water extract of abalone viscera (WEV) presented significant longer prothrombin time (PT), partial thromboplasmatin time (APTT), and thrombin time (TT) than other abalone extracts. In addition, the platelet aggregation process was inhibited by WEV as well. The antithrombotic potential of WEV was further investigated in animal studies which revealed that WEV prolonged tail bleeding time, APTT but not PT and TT and showed no effect on the platelet aggregation and platelet number. The WEV treated rats presented lower cholesterol and triglyceride level than the control group although the difference was not statistically significant.
Results of this study indicate the antithrombotic activity of abalone extracts, especially WEV, and may contribute to the further study in this field.
Hawthorn berry extract
Handbook of nutrition in Heart health
The growing body of evidence suggests that aggressive treatment for the risk factor management will improve survival and reduce the Cardiac events. It is well known Mediterranean diets enriched in plant foods are associated with positive health outcomes in reducing risk factors of Cardiovascular Disease (CVD). This review summarizes plant bioactive nutrients such as resistant starch, omega-3 fatty acids source from walnuts, avocados, coenzyme Q10, hawthorn berry fruit extract, curcumin/curcuminoids, lycopene, gugulipid and gotu kala plant sources impact on cardio-metabolic risk factors.
These plant sources of bioactive nutrients exhibited protective effects against hyperglycemia, hyperlipidemia, inflammation and oxidative stress, known risk factors for CVD and diabetic complications, in cell culture, animal studies and some human studies. This review provides information on plant bioactive nutrients, with a particular focus on active nutrients involved in lipid, carbohydrate and metabolic pathways and their potential health benefits in relation to the prevention and treatment of risk factors for hypertension, endothelial function, insulin resistance, type 2 diabetes, weight management, microalbuminuria, hypercoagulability, inflammation, abnormal thrombolysis, increased oxidative stress and CVD.
Introduction: Crataegus species (common name is Hawthorn) are medicinal plants, which have flavonoids, triterpene acids, proanthocyanidins, and organic acids as main constituents, used in the treatment of Cardiovascular Diseases. One of the main causes of multiple Cardiovascular Diseases is intravascular Thrombosis and current agents, which are used for the treatment and prevention of Thrombosis, have some side effects. Therefore, new antithrombotic and Thrombolytic agent s are still needed.
Materials and Methods: Antithrombotic function of ethanol extract of Crataegus orientalis (COE) leaves was investigated in carrageenan-induced mice tail Thrombosis model. Mice were injected with 40 μl (1%) carrageenan (Type I) dissolved in physiological saline by intraplantar administration in the right hind paw. After carrageenan injection, the extract was administered at the doses of 100, 200, and 300 mg/kg. Heparin was used as a positive control (10 and 100 IU). The length of tail-Thrombosis was measured at 24th, 48th, and 72nd hours.
Results and Conclusion: 100 mg/kg COE and 10 IU heparin were not significant when compared to control groups at the time interval (24–72 h) that results was obtained. At 24th hour, both 200 and 300 mg/kg of COE showed a significant antithrombotic activity (p < 0.05 and p < 0.01, respectively). However, 200 mg/kg COE lost its significance and there was a decrease in the significance values of 300 mg/kg COE (p < 0.05) at 48 and 72 h. From these results, it was concluded that COE significantly inhibited carrageenan-induced mice tail Thrombosis in vivo.
Context: Crataegus species are widely used as herbal medicines for preventing Cardiovascular Diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq. (Rosaceae) and C. davisii Browicz on Thrombosis, which is an important mechanism in CVDs.
Objective: The purpose of this study was to investigate the antithrombotic effects of ethanol extracts of Crataegus monogyna (CMEx) and C. davisii (CDEx) leaves by using the carrageenan-induced tail Thrombosis model.
Materials and methods: The hind paw of each mouse was injected with 1% Type I carrageenan to induce Thrombosis. CMEx was tested at the doses of 100, 200, and 300 mg/kg and CDEx at the dose of 50, 100, 200, and 300 mg/kg in comparison with heparin. The lengths of tail Thrombosis were measured at the 24, 48, and 72 h.
Results: Does of 200 and 300 mg/kg CMEx showed significant effects (p < 0.01; p < 0.001) at 24 h when compared with the control group. The antithrombotic activity of 200 and 300 mg/kg CMEx showed a decrease at 48 and 72 h but the activity of 300 mg/kg dose of CMEx was still significant (p < 0.01). The activities of 50 and 100 mg/kg doses of CDEx were significant (p < 0.001; p < 0.01) between 24 and 72 h whereas 200 and 300 mg/kg CDEx did not show any significance.
Discussion and conclusions: CMEx and CDEx significantly inhibited the carrageenan-induced mouse tail Thrombosis. Based on these results, it was concluded that CDEx and CMEx may potentially be used as therapeutic agents or complementary treatments against Thrombosis.
AN OVERVIEW: NATURAL HERBS AS AN ATHERO-ThrombolyticS
Atherosclerosis is the preliminary lipid disorder in which Arterial blood vessels become hard and thicken due to multiple Plaque formation within blood vessels. These soft multiple Plaques suddenly ruptures out, leading to the formation of thrombus that rapidly slow down or stop the blood flow and obstruct the oxygen supply to the targeted tissues. These free floating thrombi can be circulated anywhere in the Cardiovascular system including lung, brain, Heart or Deep veins of leg and leads to serious complications as atherothrombotic Diseases (Myocardial or cerebral Infarction), Coronary Artery Diseases (CAD), peripheral vascular Diseases, Pulmonary Thrombosis, cerebro-vascular Disease and Heart failure.
Pulmonary Thrombosis is a inexorable condition commonly appear in Covid -19 pneumonia patients due to fully or partially block blood supply to Artery of lung and is characterized by inexplicable breathing difficulties, hemoptysis and chest pain. Similarly cardiac arrhythmias is on rise worldwide and is leading cause of morbidity, mortality and disabilities, is associated with shortness of breath, synapse, angina or finally even death. A Cardio vascular Disease (CVD) is the highly implacable Disease and often impacting most productive and precious years of individuals throughout the world and hence requires very accurate diagnosis and treatment. Commonly used conventional antithrombotic drugs such as t-PA, Urokinase, Streptokinase, Ateplase, Anisteplase and so forth, play deciding role in CVD management and other related disorders.
However, available Thrombolytics still have noticeable shortcomings including bleeding, lysis of hemolytic plug, antigenicity, defective Coagulation , gastrointestinal and cerebral hemorrhage. In view of the inadequacies of conventional Thrombolytic s, efforts have made to understand significant value of herbal drugs for treating Coronary Arterial Disease and related problems. As diabetes mellitus, hypertension, smoking cigarettes, dislipidemia, dyspnea and pneumonia are the prime causes of increasing severity of atherosclerosis and Covid -19 Diseases , includes aggregation of platelets which eventually results in thrombus formation and hypoxia.
Moreover, Covid – 19 death rate is more common among people with such Diseases and disorders. Hence food and dietary herbals with antithrombotic characteristics may be used to improve such Diseases which ultimately maintain the health and regain healthy state of mind. The present review is focused on the availability of medicinal plants that have antithrombotic , anti- platelets and fibrinolytic potential, which can be explored for the effective treatment of thrombotic Diseases , lifestyle disorders and future pandemics like Covid -19.
kaempferol
Kaempferol inhibits Thrombosis and platelet activation
The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin Clot formation, blood Clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, Thrombosis, and Coagulation in ICR (Imprinting Control Region) mice and SD (Sprague–Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (Clot ting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation.
Moreover, kaempferol protected against Thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboEmbolism models and an FeCl3-induced carotid Arterial thrombus model. The ex vivo Anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.
lactoferrin
LF is a multifunctional glycoprotein in milk with beneficial effects on lipid metabolism. However, whether LF can inhibit the development of atherosclerosis is yet to be explored. The researchers fed 48 male apolipoprotein E?/? mice with a high-fat diet that contains 1.25 percent added cholesterol. They divided the mice into four treatment groups: the group given distilled water (HFCD), the group given 2 mg/mL LF solution, the group given 10?mg/mL LF (MLF) and the group given 20?mg/mL LF (HLF) for 12 weeks. The researchers conducted glucose tolerance tests (OGTT) at weeks 0, 4, 8 and 12 and measured serum, liver and fecal lipid levels at the end of the experiment.
They also conducted a pathological examination of the livers, whole aortas and aortic sinuses of the mice and measured the expression of proteins related to cholesterol synthesis, absorption and excretion. The researchers reported no significant difference between the body weight, food intake and OGTT results of the four groups. Compared with the HFCD group, the MLP and HLF groups had significantly reduced serum and liver cholesterol levels but significantly increased fecal cholesterol content. Treatment with LF alleviated hepatic steatosis and lipid droplet formation, as evident in the MLF group.
LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. LF decreased the expression of HMG-CoA reductase — a rate-limiting enzyme involved in cholesterol synthesis — in the liver but increased the expression of cholesterol 7-alpha hydroxylase, a rate-limiting enzyme involved in the synthesis of bile acid from cholesterol. LF also decreased the expression of Niemann-Pick C1-like 1 protein, which binds to a critical mediator of cholesterol absorption, in the intestines. Based on these findings, the researchers concluded that lactoferrin alleviates atherosclerosis by decreasing cholesterol synthesis and absorption and increasing cholesterol excretion.
Lagerstroemia speciosa
Thrombolytic activity of Lagerstroemia speciosa Leaves
Aim: to investigate the Thrombolytic activity of Lagerstroemia speciosa leaf extract.
Methods: Thrombolytic activity assayed by an in vitro Thrombolytic activity model performed on 10 apparently healthy subjects (both male and female), where the Clotlysis ability of methanolic extract of Lagerstroemia speciosa leaves compared with Streptokinase a positive control and saline water as a negative control.
Result: Fraction of methanolic extract of Lagerstroemia speciosa exhibited significant percentage (%) of Clotlysis of 25.42% compared to positive control streptokinase of 31.06% loss of Clo while the negative control saline water showed 3.81% Clotlysis ability.
Conclusion: Thepresentinvestigationrevealedthatthemethanolextracts of the leaves of Lagerstroemia speciosa possess potent Thrombolytic properties may refer to the treatment of Cardiovascular Diseases.
antithrombotic and antihemolytic effects of Lagerstroemia speciosa (Lythraceae) aqueous extract
Introduction: Aqueous extract of Lagerstroemia speciosa (EALS) (Lythraceae) is widely used to treat diabetes. This plant has been shown an in vitro Thrombolytic activity that indicates its potential to prevent the formation of blood Clot s in vivo. Thus, this study was undertaken to evaluate the antithrombotic and antihemolytic effects of EALS.
Methods: Rats of both sexes (200 ± 5 g) were divided into five groups of six animals. Each group received orally distilled water, EALS (250, 500, 1000 mg/kg), and acetylsalicylic acid (100 mg/kg) for five days. After treatment, the FeCl3-induced Arterial thrombus formation method was used to determine occlusion time. A coagulometer was used to detect activated partial thromboplastin time (aPTT) and prothrombin time (PT). Rabbit blood was used to determine Clotlysis activity in vitro and antihemolytic activity using the 2,2-azobis hydrochloride (2-methylpropionamidine) (AAPH) method.
Results: EALS increased the occlusion time in a dose-dependent manner. At the dose of 1000 mg/kg, EALS increased the occlusion time significantly, from 4.59 ± 2.45 minutes to 15.52 ± 2.38 minutes (P < 0.01). At high concentrations (1-4 mg/mL), EALS showed a significant increase in aPPT and PT (P < 0.05). Streptokinase and EALS (4 mg/mL) induced significant Clotlysis with percentage values of 78.48 ± 2.2 % and 49.5 ± 1.53 %, respectively (P < 0.001). EALS inhibited AAPH-induced hemolysis.
Conclusion: EALS exhibited antithrombotic and antihemolytic activities. The antithrombotic property of the plant could be attributed to its Anticoagulant and Thrombolytic activities. Regular consumption of L. speciosa leaves may prevent or treat thrombotic Diseases.
Leonurus japonicus Sweet extract
Leonurus japonicus Houtt. is a herbaceous annual of the Lamiaceae family with pantropical distribution; it is called motherwort in China. It plays important roles in anticoagulation and antioxidation. This study aimed to explore the optimization of ultrasound-assisted extraction of multiple compounds from motherwort as well as their antioxidant and antiCoagulation activities using response surface methodology. Box–Behnken design was employed to optimize three significant influences, namely extraction time, extraction temperature and ethanol concentration. The optimum extraction parameters acquired based on a combination of the yield of the target compounds and their antioxidant and anti coagulation activities were an extraction time of 38.2 min, an extraction temperature of 30.0 °C, an ethanol concentration of 48.9% (v/v), a solid–liquid ratio of 30.0 mL g−1 and an ultrasonic power of 500.0 W.
Under the optimal conditions, the maximal yield of the antiCoagulation and antioxidant compounds of motherwort was 0.994%; the thrombin time was 19.872 s; prothrombin time was 8.270 s; the activated partial thromboplastin time was 15.535 s; the fibrinogen was 1.420 g L−1; and the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity was 1.503 mg mL−1. The optimized conditions model showed a good correlation between the predicted and experimental values. According to the results of our study, the optimization extraction significantly enabled study of the antiCoagulation and antioxidant activities of compounds in motherwort; this may contribute to future research on the pharmacological activities of motherwort.
Thrombus is considered to be the pathological source of morbidity and mortality of Cardiovascular Disease and thrombotic complications, while oxidative stress is regarded as an important factor in vascular endothelial injury and thrombus formation. Therefore, antioxidative stress and maintaining the normal function of vascular endothelial cells are greatly significant in regulating vascular tension and maintaining a nonthrombotic environment. Leonurine (LEO) is a unique alkaloid isolated from Leonurus japonicus Houtt (a traditional Chinese medicine (TCM)), which has shown a good effect on promoting blood circulation and removing blood stasis.
In this study, we explored the protective effect and action mechanism of LEO on human umbilical vein endothelial cells (HUVECs) after damage by hydrogen peroxide (H2O2). The protective effects of LEO on H2O2-induced HUVECs were determined by measuring the cell viability, cell migration, tube formation, and oxidative biomarkers. The underlying mechanism of antioxidation of LEO was investigated by RT-qPCR and western blotting.
Our results showed that LEO treatment promoted cell viability; remarkably downregulated the intracellular generation of reactive oxygen species (ROS), malondialdehyde (MDA) production, and lactate dehydrogenase (LDH); and upregulated the nitric oxide (NO) and superoxide dismutase (SOD) activity in H2O2-induced HUVECs. At the same time, LEO treatment significantly promoted the phosphorylation level of angiogenic protein PI3K, Akt, and eNOS and the expression level of survival factor Bcl2 and decreased the expression level of death factor Bax and caspase3. In conclusion, our findings suggested that LEO can ameliorate the oxidative stress damage and insufficient angiogenesis of HUVECs induced by H2O2 through activating the PI3K/Akt-eNOS signaling pathway.
Licorice root extract
Peroxynitrite (ONOO−) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia -reperfusion injury. However, the roles of ONOO− in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in Ischemic Diseases brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO− could directly mediate the activation and release of HMGB1 in Ischemic Diseases brains with delayed t-PA treatment.
With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO−) was positively correlated with HMGB1 level in acute Ischemic Diseases Stroke patients. Hemorrhagic transformation and t-PA-treated Ischemic Diseases Stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO− decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in Ischemic Diseases rat brains with delayed t-PA treatment. ONOO− donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro.
Those results suggest that ONOO− could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO− production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in Ischemic Diseases Stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO− production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in Ischemic Diseases brains.
Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the Ischemic Diseases Stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO−/HMGB1/TLR2 signaling cascades.
thrombin inhibition therapy is a practical strategy to reduce thrombotic and Cardiovascular risks via blocking the formation of blood Clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC50 = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin -mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a Ki value of 12.23 μM.
Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents.
Nutritional and therapeutic potential of Glycyrrhiza glabra L. roots
This study was aimed to estimate the antioxidant , anti-diabetic, anti-amnesic, anti-biofilm, Thrombolytic, hemolytic, and cytotoxic effects of G. glabra root extracts for nutritive and medicinal purpose. antioxidant, alpha amylase, antiglycation, anti-amnesic, cytotoxic, Thrombolytic and antibiofilm assays were performed.
In the current research, G. glabra root extracts showed significant antioxidant (80.96 mg GAE/100 g TPC, 38.96 mg CE/100 g TFC, 46% DPPH scavenging), antidiabetic (75% antiglycation, 38.7% α-amylase inhibition ), anti-amnesic (5.5%), hemolytic (19.46%), Thrombolytic (35.4%) and antibiofilm (72% P. multocida, 51.57% S. aureus inhibition ) activities. G. glabra root extracts have remarkable activity to fight against oxidative stress, hyperglycemia, blood Coagulation, bacterial growth, DNA damage and memory enhancing ability that ensure its uses in food and pharmaceutical industries.
Possible Pharmacological Basis for antithrombotic Glycyrrhiza Glabra in Sprague Dawley Rats
It has been previously identified that 3-aryl comarin derivative, GU-7 isolated from Liquorice posses Antiplatelet activity. It inhibits platelet aggregation by increasing intraplatelet cyclic AMP concentration. Here we report the in-vivo effects of extract of Glycyrrhiza glabra and also the combined effect with Vitamin K and Heparin.
Extract of Glycyrrhiza glabra increased the bleeding time when given in the doses of 180 mg/kg and 360 mg/kg. blood loss was evaluated 60 minute later as a function of absorbance at 540 nm due to hemoglobin content in water solution. Altogether data indicates that Glycyrrhiza glabra is an effective anti thrombotic agent in vivo, which may account for its known pharmacological properties.
Ligusticum chuam.iong Hort. root extract
Tao-Hong-Si-Wu decoction (TSD) as a traditional chinese medicine (TCM) has been developed to treat thrombotic Diseases for hundreds of years, and vascular dementia (VD) is a cognitive dysfunction syndrome caused by cerebral Embolism . In this study, the protective effect of TSD on memory impairment and brain damage in rat model of VD induced by middle cerebral Artery occlusion (MCAO) was investigated. The study showed that rats in MCAO treatment with TSD for 14 days significantly improved behavioral function, increased densities of neuron, and induced angiogenesis in the brain compared with model rats. TSD also adjusted the neurotransmitter levels, reduced the content of endothelin-1 (ET-1), and induced the activities of vascular endothelial growth factor (VEGF) in hippocampus.
Moreover, the immunohistochemical staining and western blotting results also revealed that TSD decreased apoptosis via upregulated B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio. These results demonstrated TSD possesses neuroprotective and antidementia properties by preventing the loss of neural cells, adjusting brain neurotransmitter, promoting cerebral blood circulation, and decreasing apoptosis. These results suggested that TSD might be developed as an effective drug for the prevention of VD.
igusticum chuanxiong is a popular Chinese herb for Cardiovascular Diseases in China. However, its use is limited by lack of a scientific foundation. The present study aims to establish the pharmacological basis of the therapeutic effects of Ligusticum chuanxiong. Among 17 major constituents identified in Ligusticum chuanxiong. 6 were orally absorbable as predicted using a Caco-2 colonic cell model. Subsequent screening on vasorelaxation. the most widely examined effect of the herb, showed that absorbable constituents ligustilide. senkyunolide A and butylideneph thalide had relaxing effects comparable to the parent herb. The same three constituents also possessed similar anti-platelet aggregation and anti-thrombotic profiles to the parent herb. Ligusticum chuanxiong was found to have vasorelaxing, platelet -inhibitory and anti-thrombotic actions.
These effects were most likely due to the combined contribution of the three major absorbable constituents ligustilide. senkyunolide A and butylidenephthalide. Key words: Ligusticum chuanxiong, vasorelaxation, platelet, Thrombosis
Lonicerae Japonicae Flos extract
Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated.
Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects , including inhibition of inflammation, pyrexia, viruses, and bacteria, immunoregulation, and protection of the liver, nervous system, and Heart, with a focus on the potential efficacy of LJF on coronavirus Disease–2019 based on network pharmacology so as to fully underpin the utilization of LJF as a medicinal herb and a favorable nutraceutical in daily life.
N-Acetylcysteine
Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi
Background: Platelet cross-linking during Arterial Thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet -rich thrombi and restore vessel patency in acute thrombotic disorders such as Ischemic Diseases Stroke , acute Coronary syndrome, or acute limb ischemia . N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and Arterial recanalization.
Methods: Experimental models of thrombotic Stroke induced by either intra-Arterial thrombin injection or ferric chloride application followed by measurement of cerebral blood flow using a combination of laser Doppler flow metry and MRI were performed to uncover the effects of NAC on Arterial thrombi. To investigate the effect of NAC on larger vessels, we also performed ferric chloride–induced carotid Artery Thrombosis . In vitro experiments were performed to study the molecular bases of NAC Thrombolytic effect, including platelet aggregometry, platelet -rich thrombi lysis assays, thromboelastography (ROTEM), and high-shear VWF string formation using microfluidic devices. We also investigated the putative prohemorrhagic effect of NAC in a mouse model of intracranial hemorrhage induced by in situ collagenase type VII injection.
Results: We demonstrated that intraVenous NAC administration promotes lysis of Arterial thrombi that are resistant to conventional approaches such as recombinant tissue-type plasminogen activator, direct thrombin inhibitors, and antiplatelet treatments. Through in vitro and in vivo experiments, we provide evidence that the molecular target underlying the Thrombolytic effects of NAC is principally the VWF that cross-link platelet s in Arterial thrombi. Coadministration of NAC and a nonpeptidic GpIIb/IIIa inhibitor further improved its Thrombolytic efficacy, essentially by accelerating thrombus dissolution and preventing reThrombosis . Thus, in a new large-vessel Thromboembolic Stroke model in mice, this cotreatment significantly improved Ischemic Diseases lesion size and neurological outcome. It is important to note that NAC did not worsen hemorrhagic Stroke outcome, suggesting that it exerts Thrombolytic effects without significantly impairing normal hemostasis.
Conclusions: We provide evidence that NAC is an effective and safe alternative to currently available antithrombotic agent s to restore vessel patency after Arterial occlusion.
Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report
Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening Disease resulting in systemic microvascular Thrombosis . The Disease is caused by excessive platelet (PLT) adhesion to ultra-large (UL) von Willebrand factor (VWF) multimers inadequately cleaved by the processing enzyme ADAMTS-13. While many cases respond to plasma exchange performed with or without concurrent corticosteroids, treatment of the 10% to 20% of patients with refractory Disease is difficult. Experimental studies demonstrating that N-acetylcysteine (NAC) inhibits PLT binding to endothelial cell–secreted and anchored UL VWF multimers suggest that NAC may be useful in the treatment of TTP.
Case Report: A 44-year-old woman presented with malaise, confusion, chest and abdominal pain, and transient visual loss. Laboratory results and peripheral blood smear were consistent with TTP. The patient was begun on plasma exchange and corticosteroid treatment, but after 10 days the PLT count was still less than 10.0 × 109/L and she developed a fever. Rituximab was initiated, but the patient’s condition worsened and she became comatose. Antibiotics were initiated, but cultures remained sterile. After 3 days of coma and further clinical deterioration, treatment with NAC was begun. The patient received a loading dose of 150 mg/kg NAC intraVenous ly (IV) over 1 hour. Within 18 hours the patient awakened abruptly and began communicating with medical personnel. Plasma exchange, corticosteroids, rituximab, and NAC infusion (150 mg/kg IV over 17 hr daily × 10 days) were continued and by Day 17 the PLT count was more than 50 × 109/L. The patient fully recovered and was discharged on Day 31.
Conclusion: This is the first complete report of a TTP patient treated with NAC. NAC was a safe and effective supplementary treatment for refractory TTP in this patient.
N-acetylcysteine inhibits Thrombosis in a murine model of myeloproliferative neoplasm
Thrombosis is a major cause of mortality in patients with myeloproliferative neoplasms (MPNs), though there is currently little to offer patients with MPN beyond aspirin and cytoreductive therapies such as hydroxyurea for primary prevention. Thrombogenesis in MPN involves multiple cellular mechanisms, including platelet activation and neutrophil-extracellular trap formation; therefore, an antithrombotic agent that targets one or more of these processes would be of therapeutic benefit in MPN.
Here, we treated the JAK2V617F knockin mouse model of polycythemia vera with N-acetylcysteine (NAC), a sulfhydryl-containing compound with broad effects on glutathione replenishment, free radical scavenging, and reducing disulfide bonds, to investigate its antithrombotic effects in the context of MPN. Strikingly, NAC treatment extended the lifespan of JAK2V617F mice without impacting blood counts or splenomegaly. Using an acute Pulmonary Thrombosis model in vivo, we found that NAC reduced thrombus formation to a similar extent as the irreversible platelet inhibitor aspirin. In vitro analysis of platelet activation revealed that NAC reduced thrombin-induced platelet-leukocyte aggregate formation in JAK2V617F mice.
Furthermore, NAC reduced neutrophil extracellular trap formation in primary human neutrophils from patients with MPN as well as healthy controls. These results provide evidence that N-acetylcysteine inhibits Thrombosis in JAK2V617F mice and provide a pre-clinical rationale for investigating NAC as a therapeutic to reduce thrombotic risk in MPN.
Natto
Thrombolytic Effect of Nattokinase on a Chemically Induced Thrombosis Model in Rat
Nattokinase is a new fibrinolytic enzyme which cleaves directly cross-linked fibrin in vitro. In this study, we investigated the Thrombolytic effect of nattokinase on a thrombus in the common carotid Artery of rat in which the endothelial cells of the vessel wall were injured by acetic acid. When a section of occluded vessel was stained for CD61 antigen by immunofluorescence utilizing a monoclonal antibody, the antigen was localized around the surface of the occluded blood vessels.
This result suggests that the occlusive Thrombosis was caused by platelet aggregation . In addition, thrombolysis with urokinase (UK ; 50000IU/kg, i.v.) or tissue plasminogen activator (tPA ; 13300IU/kg, i.v.) in our model was observed to restore the blood flow over a 60 min monitoring period. The results indicate that our chemically induced model is useful for screening and evaluating a Thrombolytic agent.
We evaluated the Thrombolytic activity of nattokinase using this model and compared it with fibrino (geno) lytic enzyme, plasmin or elastase. On a molar basis, the recovery of the Arterial blood flow with nattokinase, plasmin and elastase were 62.0±5.3%, 15.8±0.7% and 0%, respectively. The results indicate that the Thrombolytic activity of nattokinase is stronger than that of plasmin or elastase in vivo.
Natto and Its Active Ingredient Nattokinase: A Potent and Safe Thrombolytic agent
Nattokinase: An Oral antithrombotic agent for the Prevention of Cardiovascular Disease
Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood–Clot dissolving protein used for the treatment of Cardiovascular Diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention.
Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.
Thrombolytic effects in vivo of Nattokinase in a Carrageenan-Induced Rat Model of Thrombosis
Background/Aims: Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and Thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo.
Methods: To establish a rat model of Thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed Thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known Thrombolytic agent, was used as a positive control.
Results: Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase.
Conclusions: Both the histological and physiological evidence from this study indicate that nattokinase exerts Thrombolytic effects in vivo.
Background: Nattokinase (NK) is a serine protease enzyme of the subtilisin family. It exhibits a strong fibrinolytic activity. The fibrinolytic enzymes from Bacillus sp. have attracted interest as Thrombolytic agent s because of their efficiency in the fibrinolytic process including plasmin activation .
Methods: In the present study, VIT garden soil was collected and subjected to isolation process in order to screen for the NK production. Screening for NK enzyme was performed by radial caseinolytic assay. The production of NK enzyme was done in two different production medium for comparative studies. The NK enzyme was purified by gel permeation chromatography. The activity of the purified NK was checked by Clotlysis and casein digestion assay. To investigate the structural basis of NK and fibrinogen interaction and also to identify the best binding mode, molecular dynamics and docking studies were performed.
Results: Based on the morphological and biochemical characterization, the isolate was identified as Bacillus sp. The overall purification fold of NK was about 3 with the specific activity of 664U/mg and 9.9% yield. Homogeneity of the purified enzyme was analyzed and confirmed by the single band obtained in SDS-PAGE. Molecular weight of the purified protease was estimated as 25 kDa. Purified NK enzyme exhibited 97% of effective Clotlysis activity. The NK was docked in to the knob region of the fibrinogen at its binding site using Dock server. A total of 26 residues of fibrinogen and 29 residues of NK constitute the interface region. However, 9 residues of fibrinogen (THR238, MET264, LYS266, ARG275, THR277, ALA279, ASN308, MET310, and LYS321) and 8 residues of NK (GLY61, SER63, THR99, PHE189, LEU209, TYR217, ASN218, and MET222) are involved in intact binding.
Conclusions: A significant amount of NK enzyme was obtained from Bacillus sp. The docking analysis revealed that the NK and fibrinogen adopt an extended binding pattern and interacts with the crucial residues to exhibit their activity.
Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood Clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intraduodenum administration of NKCP.
Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use.
Nelumbinis Stamen (Lotus)
Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the Heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.
Methods: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis.
Results: Plumula Nelumbinis is used to treat hypertension , arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological Disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects , such as protective effects against Cardiovascular Diseases , neurological Diseases , lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in Cardiovascular and neurological Diseases and perspectives on Plumula Nelumbinis research were discussed.
Conclusion: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of Cardiovascular and neurological Diseases , have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary.
Systematic chemical analysis of flavonoids in the Nelumbinis stamen
The stamen of lotus, known as Nelumbinis stamen, has been used as the folk medicine and functional food for a long time, which showed good activities of anti-ulcer, AntiThrombosis , analgesic, anti-diarrhea, strengthen uterine contraction. The bioactivities of Nelumbinis stamen were attributed to the existence of flavonoids, its characteristic chemical constituents. A reliable method for comprehensive chemical analysis of flavonoids in Nelumbinis stamen by HPLC–DAD–MS was developed for the first time. The extraction protocol of flavonoids from Nelumbinis stamen was optimized by an orthogonal design.
The chromatographic conditions were optimized, which exhibited similar level than that of the UHPLC platform allowing target compound identification in a shorter time with little solvent consumption. Moreover, similarity analysis, hierarchical clustering analysis and principal components analysis were successfully applied to demonstrate the variability of these Nelumbinis stamen samples.
Nigella sativa
The Thrombolytic and Cytotoxic effects of Nigella sativa (L.) Seeds: The Prophetic Medicine
The Water-Soluble Extract (WSE) is a crude bioactive phytoconstituent of Nigella sativa (L.) seeds discovered recently. The current findings report about the Thrombolytic and cytotoxic effects of WSE using human blood Clotlysis and brine shrimp lethality (BSL) bioassay. The Thrombolytic effect of WSE (1,666.67 µg/mL) was determined via the Clot and lysate weight measurements compared to streptokinase (STK) of 30,000 IU/mL and normal saline (NS) while the cytotoxicity of WSE (44.14-2,000 µg/mL) against vincristine sulfate (VCS;3.125-100 µg/mL). WSE has shown extremely statistically significant (p<0.0001) Clotlysis (90.00%) compared to NS (3.76%) whilst it was also significantly different (p<0.0063) to STK (72.41%) exhibiting LC50 of 1,795.90 µg/mL vs. VCS (39.25 µg/mL) in a dose-dependent manner.
The current results suggested WSE has a potent Thrombolytic effect with mild dose-dependent cytotoxicity towards brine shrimp nauplii (Artemia salina). It also suggested WSE might have enzymatic roles on thrombin, fibrin, and plasmin of blood. This pharmacological action of WSE is might be due to its antioxidant property, short-chain fatty acids and/or amino acids. Further studies are highly recommended on the enzymatic role(s) and bioactive phytoconstituents of WSE.
In vitro induction of endothelial cell fibrinolytic alterations by Nigella sativa
The effect of Nigella sativa (NS) L. oil (blackseed oil) on the fibrinolytic system of the human umbilical vein (HUV) and human uterine Arterial (HUA) endothelial cells (ECs) in culture was studied. Both of them showed a concentration-dependent increase in tissue-type plasminogen activator (t-PA). A maximum effect was achieved with 50 μg oil/ml conditioned medium (CM) (1.3±0.15 ng/104 cells/24 h vs. control 0.7±0.06 ng/104 cells/24 h, and 0.38±0.04 ng/104 cells/24 h vs. control 0.24±0.02 ng/104 cells/24 h, for HUVEC and HUA-EC, respectively).
At 100 μg/ml, there was a significant change in the amount of t-PA antigen produced by either HUVEC or HUA-EC (1.0±0.1 ng/104 cells/24 h or 0.28±0.02 ng/104 cells/24 h) as compared to control CM from cells grown under control conditions, but still less than that recorded at 50 μg oil/ml. Plasminogen activator inhibitor-type 1 increased the CM significantly and concentration-dependently in both cells. For HUVEC, the maximum effect was achieved at a concentration of 100 μg/ml (257.7±8.0 ng/104 cells/24 h vs. control 72.7±3.8 ng/104 cells/24 h). HUA-EC showed the maximum effect at a concentration of 100 μg/ml (171.6±4.4 ng/104 cells/24 h vs. control 53.8±3.7 ng/104 cells/24 h). This study suggests a role for NS oil in modulating the balance of fibrinolysis/thrombus formation by modulating the fibrinolytic potential of endothelial cells.
Evaluation of Thrombolytic properties of Nigella sativa, Capsicum frutescens and Brassica oleracea
Thrombolytic drugs are widely used for the management of cerebral Venous sinus Thrombosis patients. Several in vitro models have been developed to study Clotlysis activity of Thrombolytic drugs, but all of these have certain limitations. The present study was carried out to investigate the Thrombolytic activity, synergistic activity on thrombolysis in the aqueous extract of fruits of Nigella sativa, Capsicum frutescens, Brassica oleracea. An in vitro Thrombolytic method was used to investigate the Thrombolytic activity of plant extracts in blood sample from healthy human volunteers, along with streptokinase as a positive control and water as a negative control. Same method was also applied to assess the synergistic activity of plant extracts with streptokinase. Aqueous extract of Nigella sativa, Capsicum frutescens, Brassica oleracea showed 40.65%, 36.93%, 57.03% Thrombolytic activity and also showed 60.46%, 80.00%, 72.50% synergistic activity with streptokinase respectively.
Among the plant extracts studied Capsicum frutescens showed significant % of synergistic activity (80%) with compared to other plant extracts. The present study demonstrates that Capsicum frutescens extract showed synergistic activity with streptokinase on thrombolysis. Isolation and purification of the compound responsible for synergistic activity would be one of the best sources of herbal drugs for atherothrombotic Diseases.
Paeonia suffruticosa Andr. peel extract
antiplatelet agent s are important in the pharmacotherapeutic regime for many Cardiovascular Diseases , including thrombotic disorders . However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agent s selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets.
The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented Arterial Thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood Clot ting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.
The roots of two Paeoniaceae family members have long been used as traditional medicines in Korea, China, and Japan. Dry roots of Paeonia lactiflora and dry root bark of P. suffruticosa are used under the traditional names of Paeoniae Radix and Moutan Cortex, respectively. Both Paeoniae Radix and Moutan Cortex have been used as remedies for Cardiovascular Diseases , for improving blood circulation, or for other uses. It was postulated that both plants may contain common active constituents that contribute to inhibiting blood Coagulation and/or platelet aggregation. Eighteen compounds, which have been reported to be present in both plant medicines, were evaluated for their effects on platelet aggregation and blood Coagulation.
Paeonol (5), paeoniflorin (9), benzoylpaeoniflorin (11), and benzoyloxypaeoniflorin (12) were found to be the major common active constituents and they would collectively contribute to improving blood circulation through their inhibitory effects on both platelet aggregation and blood Coagulation. In addition, methylgallate (4), (+)-catechin (7), paeoniflorigenone (8), galloylpaeoniflorin (13), and daucosterol (16) may also take part in improving blood circulation by inhibiting ether platelet aggregation and/or blood Coagulation.
Paeonia veitchii Lynch root extract
Background: In the clinic, Naoxintong capsule (NXT) has been applied in two level prevention of Ischemic Diseases Disease . However, its mechanism of action requires further study.
Purpose: This study investigated whether NXT could affect platelet function and activation under Ischemic Diseases pathological conditions.
Materials and methods: Wistar rats were divided into six groups, sham, saline, NXT (250, 500, 1000 mg/kg), and aspirin group (10 mg/kg). For the pre-treatment assays, MI model was established after pre-administration of saline, NXT-L, NXT-M, NXT-H, and aspirin respectively for 14 days, and after surgery, there were no continuous treatments. For the post-treatment assay, rats were orally administered for 3 days after MI. FeCl3-induced Thrombosis model was applied to determine the thrombus wet weight. Bleeding time was used to assess the ability of the platelet s to develop a hemostatic plug.
Results: NXT decreased infarct size, decreased LDH, CK, and CK-MB values, and improved Cardiac function. NXT inhibited platelet s activation through reducing CD62P-positive platelet s and inhibited infarct expansion by decreasing the number of CD45-positive cells and the amount of MMP9 secreted into the Heart tissue. Mechanistically, NXT inhibited platelet s activation through decreasing ROS levels, decreasing ERK5 phosphorylation, and increasing RAC1 phosphorylation in MI rats. Pre-treatment with NXT decreased thrombus formation and had normal bleeding times.
Conclusion: NXT showed obviously preventive effects , which was associated with negative control of platelet activation . The above results provide a basis for clinically expanding application of NXT.
Cellular and Molecular Mechanisms of Antithrombogenic Plants: A Narrative Review
Heart attack, Stroke, and Deep vein Thrombosis are among the conditions that alter blood Coagulation and are modulated by antithrombogenic drugs. Natural products are an important source of antithrombogenic agent s and have been considered remarkable alternatives with greater efficacy and usually with fewer side effects. However, the efficacy and toxicity of many of these plants that are used in traditional medicine must be scientifically tested. Despite a large number of published articles that report that plants or plant-derived components may act as antithrombogenic agents, few studies have investigated the mechanism of action of medicinal plants.
This review presents the current knowledge about the major cellular and molecular mechanisms of antithrombogenic plants and their main components. Many well-established mechanisms (e.g., platelet aggregation, Coagulation factors, and thrombolysis ) are related to the antithrombogenic activity of many natural products. However, the central pathways that are responsible for their activity remain unclear.
Further studies are needed to clarify the central role of each of these pathways in the pleiotropic response to these agents.
Panax notoginseng (Burk.)F. H. Chen root extract
The classic Virchow theory suggests that blood stasis, hypercoagulability and endothelial dysfunction are three major factors that cause Venous Thrombosis (VT). It is a complicated biological process involved multi-factors. platelet plays a central role and participates in multiple links of this process. Panax notoginseng saponins (PNS), the principal constituents derived from panax notoginseng, has been widely described for its anti-platelet activity. However, its potential mechanism against platelet aggregation has not been clarified. In this present study, we evaluated the anti-platelet effects of PNS on thrombin -induced platelet activation and its possible molecular mechanism of action, and further explored the therapeutic action of PNS on thrombin induced hypercoagulability in rat.
Our results showed that PNS treatment inhibited platelet aggregation induced by thrombin, which was accompanied with over-expression of Peroxisome proliferator-activated receptor γ (PPAR-γ) protein, mRNA and upregulation of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) pathway in platelet, and this effect could be reversed by PPAR-γ inhibitor T0070907.
In vivo, PNS significantly reversed thrombin -induced hypercoagulable state in rat which was accompanied by PPAR-γ protein and mRNA upregulation in rat lung. In conclusion, these data suggested that PNS could suppress thrombin-induced platelet aggregation in vitro and effectively improve hypercoagulable state in vivo and PNS-induced activation of PPAR-γ and its downstream PI3K/Akt/eNOS pathway played the central role.
Objective
To observe the combination effects of Panax notoginseng saponins (PNS)and dual antiplatelet drugs (DAPT), and to explore the mechanism via cyclooxygenase /prostaglandin pathway.
Methods
Right carotid Artery Thrombosis was induced in Wistar rats by infiltration with 70% FeCl3, and the animals were randomly divided into sham group, model group, DAPT group and PNS + DAPT group, intragastrically treated for 4 weeks. The cerebral pia mater microcirculation was observed in vivo after anesthetizing by anatomical microscope. The wet weight of carotid Artery Thrombosis was measured. Gastric mucosal injury was observed by hematoxylin and eosin staining. platelet aggregation rate was detected with adenosine diphosphate -induced turbidimetry. platelet CD62p expression was detected by flow cytometry. Concentrations of 6-Ketoprostaglandin F1 alpha, prostaglandin E2 in gastric mucosa and thromboxane B2, 6-Ketoprostaglandin F1 alpha, tissue plasminogen activator, plasminogen activator inhibitor, and fibrin fragment D in the plasma were measured by radioimmunoassay.
Results
PNS and DAPT increased the blood flow volume of cerebral pia mater and decreased erythrocyte aggregation and leukocyte adhesion of model rats. Compared to DAPT, PNS and DAPT further reduced the weight of carotid Artery Thrombosis with enhanced inhibition of platelet aggregation , increased tissue plasminogen activator levels and decreased fibrin fragment D levels. PNS and DAPT alleviated gastric injury induced by dual antiplatelet drugs and upregulated the expression of 6-Ketoprostaglandin F1 alpha in the gastric mucosa compared with DAPT.
Conclusions
PNS combined with DAPT increased anti-Thrombosis effects of DAPT and mitigated DAPT-related gastric injury. The underlying mechanisms may be associated with enhanced antiplatelet aggregation and activation of the fibrinolytic system and up-regulation of 6-Ketoprostaglandin F1 alpha expression in gastric mucosa.
Ethnopharmacological significance: Panax notoginseng (Burk.) F. H. Chen (Araliacea) is traditionally used for its hemostatic and Cardiovascular effects when raw and as a tonic when steamed.
Aim of the study: This study aims to compare the effects of raw and steamed Panax notoginseng, Panax ginseng C. A. Meyer and Panax quinquefolium Linn. on platelet aggregation and plasma Coagulation.
Materials and methods: Effects on collagen-induced platelet aggregation were investigated using a platelet aggregometer, while the plasma Coagulation times (prothrombin time, activated partial thromboplastin time and thrombin time) were determined using a blood Coagulation analyzer. The data was corroborated with ex vivo platelet aggregation and in vivo rat bleeding time.
Results: Raw and steamed Panax notoginseng significantly inhibit platelet aggregation and plasma Coagulation. Steamed Panax notoginseng has significantly more potent antiplatelet and Anticoagulant effects than the raw extract, and the antiplatelet and Anticoagulant effects increase with increasing steaming durations. Comparing the three common Panax species, Panax notoginseng has higher antiplatelet effect than Panax ginseng and Panax quinquefolium. The in vitro antiplatelet and Anticoagulant effects are positively translated into a prolongation of in vivo rat bleeding time after oral administration of the raw and steamed extracts.
Conclusion: The results indicate that the three common Panax species affect platelet aggregation and plasma Coagulation differently, with steamed Panax notoginseng showing the greatest antiplatelet and Anticoagulant effects . Panax notoginseng may be a good source of lead compounds for novel antiplatelet and Anticoagulant therapeutics.
Objective: This study was designed to investigate the effect of Panax notoginseng saponin (PNS) on platelet adhesion to injured endothelial cells (ECs) and platelet activation induced by injured ECs, and to explore its underlying mechanisms.
Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with aspirin (ASA,15 μg/mL) or PNS (160 μg/mL), or neither, were exposed to oxidized low-density lipoprotein (ox-LDL,80 mg/L) for 16 h. platelet s were then added and co-cultured with HUVECs for 5 min. platelet adhesion to ECs, platelet CD62p expression, and HUVEC apoptosis were assessed by fluorescence activated cell sorting (FACS)·Supernatant concentration of 6-keto-PGF1α and thromboxane 2 (TXB2) were measured by radioimmunoassay. Cyclooxygenase-1 (COX-1) and COX-2 protein expression were measured by western blotting.
Results: The inhibitory effect of PNS on platelet activation was similar to ASA, but the inhibitory effect of PNS on platelet adhesion to ECs was superior to ASA. PNS modulated COX-2 expression, and increased 6-keto-PGF1α concentration in HUVECs, while down-regulated COX-1 expression and decreased supernatant TXB2 concentration in platelet s. Co-culturing of injured HUVECs with platelet s increased HUVEC apoptosis induced by ox-LDL compared with HUVECs cultured without platelet s; ASA increased HUVEC apoptosis induced by ox-LDL when cultured without platelets, while decreased the apoptosis when co-cultured with platelets.
Conclusions: EC protection by ASA is closely associated with its inhibitory effect on platelet activation . PNS is superior to ASA in protecting ECs and in inhibiting platelet adhesion to injured ECs, and the regulation of COX pathway in both ECs and platelet s might be the underlying mechanisms of PNS.
Panax ginseng
Covid -19 and Panax ginseng: Targeting platelet aggregation , Thrombosis and the Coagulation pathway
Coronavirus Disease 2019 (Covid -19 ) not only targets the respiratory system but also triggers a cytokine storm and a series of complications, such as gastrointestinal problems, acute kidney injury, and Myocardial ischemia . The use of natural products has been utilized to ease the symptoms of Covid -19 , and in some cases, to strengthen the immune system against Covid -19. Natural products are readily available and have been regularly consumed for various health benefits. Covid -19 has been reported to be associated with the risk of thromboEmbolism and Deep vein Thrombosis.
These thrombotic complications often affects mortality and morbidity. Panax ginseng, which has been widely consumed for its various health benefits has also been reported for its therapeutic effects against Cardiovascular Disease, Thrombosis and platelet aggregation . In this review, we propose that P. ginseng can be consumed as a supplementation against the various associated complications of Covid -19, especially against Thrombosis.
We utilized the network pharmacology approach to validate the potential therapeutic properties of P. ginseng against Covid -19 mediated Thrombosis , the Coagulation pathway and platelet aggregation. Additionally, we aimed to investigate the roles of P. ginseng against Covid -19 with the involvement of platelet -leukocyte aggregates in relation to immunity-related responses in Covid -19.
Coronavirus has been spreading rapidly around the world since it broke out in China in 2019. Respiratory Diseases caused by coronavirus infection cause various Diseases ranging from asymptomatic subclinical infections to severe pneumonia and Cardiovascular complications, leading to death. In this regard, natural products are being studied to prevent various Diseases caused by Covid -19.
In current review, we would like to present mechanisms related to the inhibition of Heart Disease in ginseng and ginsenoside against SARS-CoV-2. In many previous studies, ginseng and ginsenoside are known to have antioxidant, blood flow improvement, improvement of vascular and Heart function, blood pressure control, suppression of Myocardial Infarction and Heart failure, and antiarrhythmia. Therefore, ginseng and ginsenoside have a possibility to suppress Cardiovascular complications caused by Covid -19. Many of research provide evidence for ginseng and ginsenoside as treatments for the risk of Cardiovascular complications.
However, in this review, more specific contents on the proposition of the efficacy of ginseng and ginsenoside for Covid -19 should be presented. Therefore, we hope that researches to reduce Cardiovascular complications of ginseng and ginsenoside for Covid -19 should be presented to reduce mortality for Covid -19.
Potential benefits of ginseng against Covid -19 by targeting inflammasomes
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) is the pathogenic virus that causes coronavirus Disease 2019 (Covid -19 ), with major symptoms including hyper-inflammation and cytokine storm, which consequently impairs the respiratory system and multiple organs, or even cause death. SARS-CoV-2 activates inflammasomes and inflammasome-mediated inflammatory signaling pathways, which are key determinants of hyperinflammation and cytokine storm in Covid -19 patients.
Additionally, SARS-CoV-2 inhibits inflammasome activation to evade the host’s antiviral immunity. Therefore, regulating inflammasome initiation has received increasing attention as a preventive measure in Covid -19 patients. Ginseng and its major active constituents, ginsenosides and saponins, improve the immune system and exert anti-inflammatory effects by targeting inflammasome stimulation. Therefore, this review discussed the potential preventive and therapeutic roles of ginseng in Covid -19 based on its regulatory role in inflammasome initiation and the host’s antiviral immunity.
Ginseng, a promising choice for SARS-CoV-2 : A mini review
The current Covid -19 pandemic has changed the entire world and bought so many unprecedented challenges to the scientific community. More than 5 million people died due to the SARS-CoV-2 outbreak. For many thousands of years, ginseng, the traditional herb has been used for various infectious Diseases by traditional healers. Ginseng showed promising antiviral effects by modulating both natural and acquired immunity. Ginseng might be used as a potential therapeutic agent to prevent SARS-CoV-2 infection along with the vaccine.
In this current review, we offer an alternative approach for SARS-CoV-2 prevention during this unprecedented pandemic.
Korean Red Ginseng, a regulator of NLRP3 inflammasome, in the Covid -19 pandemic
Coronavirus Disease 2019 (Covid -19 ) exhibits various symptoms, ranging from asymptomatic to severe pneumonia or death. The major features of patients in severe Covid -19 are the dysregulation of cytokine secretion, pneumonia, and acute lung injury. Consequently, it leads to acute respiratory distress syndrome, disseminated intravascular Coagulation, multiple organ failure, and death. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ), the causative virus of Covid -19, influences nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3), the sensor of inflammasomes, directly or indirectly, culminating in the assembly of NLRP3 inflammasome and activation of inflammatory caspases, which induce the inflammatory disruption in severe Covid -19. Accordingly, the target therapeutic s for inflammasome has attracted attention as a treatment for Covid -19.
Korean Red Ginseng (KRG) inhibits several inflammatory responses, including the NLRP3 inflammasome signaling. This review discusses the role of KRG in the treatment and prevention of Covid -19 based on its anti-NLRP3 inflammasome efficacy.
Ginsenoside Rg1 inhibits platelet activation and Arterial Thrombosis
Introduction: Derived from the root of Panax ginseng C.A.Mey, Panax notoginsenosides (PNS) is a widely used herbal medicine to treat atherothrombotic Diseases in Asian medicine. Ginsenoside Rg1 is one of the main compounds responsible for the pharmaceutical actions of PNS. As platelets play pivotal roles in atherothrombogenesis, we therefore studied the effect of Rg1 on platelet activation and its underlying mechanisms.
Materials and Methods: Human platelet s are obtained from healthy subjects. platelet activation and the inhibition of Rg1 were assessed by Born aggregometer, flow cytmetry, flow chamber and western blot. The in vivo Thrombosis model was induced by 10% FeCl3 on mesenteric arterioles of wild type B57/b6 mice.
Results: Rg1 significantly inhibited platelet aggregation induced by thrombin, ADP, collagen and U46619, e.g., aggregation rate stimulated by 0.1 U mL- 1 thrombin was decreased 46% by Rg1. Rg1 also reduced thrombin (0.1 U mL- 1)-enhanced fibrinogen binding and P-selectin expression of single platelet by 81% and 66%, respectively. Rg1 affected αIIbβ3-mediated outside-in signaling as demonstrated by diminished platelet spreading on immobilized fibrinogen. Rg1 also decreased the rate of Clot retraction in platelet rich plasma. Furthermore, Rg1 decreased platelet adhesion on collagen surface under a shear rate correlated to the Arterial flow (1000 s- 1) by approximately 70%. Western blot showed that Rg1 potently inhibited ERK phosphrylation. The in vitro findings were further evaluated in the mouse model of in vivo Arterial Thrombosis, and Rg1 was found to prolong the mesenteric Arterial occlusion time (34.9 ± 4.1 min without and 64.3 ± 4.9 min with Rg1; p < 0.01).
Conclusions: Rg1 inhibits platelet activation via the inhibition of ERK pathway, and attenuates Arterial thrombus formation in vivo.
Polygoni Multiflori Radix extract
Clinical effect of Zhongfeng Fangzhiling Granule on acute cerebral Thrombosis
To explore clinical effect of Zhongfeng Fangzhiling Granule(Radix Pseudostellariae,Radix Polygoni Multiflori praeparata cum succo glycines sotae,Hirudo,etc.) on acute cerebral Thrombosis.
Methods: 72 patients were randomly divided into 2 groups.The treatment group was treated with Zhongfeng Fangzhiling Granule,the control group was treated with Zhilong Xuetong Capsule.The treatment effects between two groups were compared.
Results: The effect in treatment group was superior to that in control group.
Conclusions: Zhongfeng Fangzhiling Granule has significiant therapeutic effect on patients with acute cerebral Thrombosis ,and the preparation method is simple,so it will be a prospective herb granule.
Currently, an increasing number of patients are seriously affected by acute thrombotic events. In China, Polygonum multiflorum (PM) is commonly used to treat Diseases associated with Thrombosis . Our previous work showed that PM could inhibit the platelet aggregation that plays a key role in the pathogenesis of Thrombosis. However, the constituents of PM are complicated, and quality control methods cannot completely ensure the quality and clinical efficacy.
In an attempts to explore this problem, we constructed a direct bioassay method to evaluate the antiplatelet aggregation effects of PM. To ensure the precision and reliability of this bioassay, we optimized and standardized the experimental conditions and then tested the standardized bioassay by analyzing 10 PM samples. Additionally, we combined chemical and biological evaluation methods to identify antiplatelet aggregation markers. The evaluation indicated that 10 samples of PM could inhibit platelet aggregation and there was a notable difference in biopotency between the different PM groups.
Chemical fingerprints revealed variations in the contents of the 7 main peaks. Trans-2,3,5,4′-tetrahydroxy-stilbene-2-O-β-d-glucoside and catechin might be active constituents of antiplatelet aggregation as determined by spectrum-effect relationships. This work indicates that bioassay and spectrum-effect relationships are useful tools to associate sample quality with the potential chemical markers linked to the clinical effects of Traditional Chinese Medicines.
Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on Ischemic Diseases Stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on Ischemic Diseases Stroke.
Proton nuclear magnetic resonance (1H NMR) based metabolomics analysis disclosed that HSW could relieve Stroke rats suffering from the ischemia /reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1β, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving Ischemic Diseases Stroke. Further study to develop HSW as an effective therapeutic agent to treat Ischemic Diseases Stroke is warranted.
Cellular and Molecular Mechanisms of Antithrombogenic Plants: A Narrative Review
Heart attack, Stroke, and Deep vein Thrombosis are among the conditions that alter blood Coagulation and are modulated by antithrombogenic drugs. Natural products are an important source of antithrombogenic agents and have been considered remarkable alternatives with greater efficacy and usually with fewer side effects. However, the efficacy and toxicity of many of these plants that are used in traditional medicine must be scientifically tested. Despite a large number of published articles that report that plants or plant-derived components may act as antithrombogenic agents, few studies have investigated the mechanism of action of medicinal plants.
This review presents the current knowledge about the major cellular and molecular mechanisms of antithrombogenic plants and their main components. Many well-established mechanisms (e.g., platelet aggregation, Coagulation factors, and thrombolysis ) are related to the antithrombogenic activity of many natural products. However, the central pathways that are responsible for their activity remain unclear. Further studies are needed to clarify the central role of each of these pathways in the pleiotropic response to these agents.
Poria cocos( Schw.) Wolf extract
In this work, a water-insoluble β-d-glucan (PCSG), isolated from Poria cocos, was carboxymethylated to create a water-soluble derivative named as CP. After free amino groups have been introduced, CP was covalently immobilized onto PU surface. The hydrophilicity and the concentration of carboxyl group on the modified PU surface were determined. The fibrinogen and albumin adsorption to the surface, in vitro blood compatibility, and antibacterial activity of the surface against Pseudomonas aeruginosa were evaluated.
The water contact angle measurement indicated that the hydrophilicity of PU surface increased after modification. The fibrinogen adsorption of the modified PU surface decreased 51.5%, compared with control PU. CP immobilization could prolong the blood Coagulation time was suggested by APTT experiment. Antibacterial activity experiments indicated that CP modified surface obviously suppressed the growth of P. aeruginosa. Thereby, CP immobilization improves blood compatibility of PU surface and introduces special antibacterial bioactivity.
anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko
Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and Stroke. However, the effect of KOK on platelet activity has not been clarified.
Materials and methods: To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca2+ increase, and PLCγ and Akt activation . To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboEmbolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect.
Results: KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelet s in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca2+ elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against Thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect.
Conclusions: These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet -associated Cardiovascular Diseases.
Poria cocos is a traditional Chinese medicine (TCM) that can clear dampness, promote diuresis, and strengthen the spleen and stomach. Poria cocos has been detected in many TCM compounds that are used for Covid -19 intervention. However, the active ingredients and mechanisms associated with the effect of Poria cocos on Covid -19 remain unclear. In this paper, the active ingredients of Poria cocos, along with their potential targets related to Covid -19, were screened using TCMSP, GeneCards, and other databases, by means of network pharmacology.
We then investigated the active components, potential targets, and interactions, that are associated with Covid -19 intervention. The primary protease of Covid -19, Mpro, is currently a key target in the design of potential inhibitors. Molecular docking techniques and molecular dynamics simulations demonstrated that the active components of Poria cocos could bind stably to the active site of Mpro with high levels of binding activity.
Pachymic acid is based on a triterpene structure and was identified as the main component of Poria cocos; its triterpene active component has low binding energy with Mpro. The pachymic acid of Mpro activity was further characterized and the IC50 was determined to be 18.607 μmol L−1. Our results indicate that pachymic acid exhibits a certain inhibitory effect on the Mpro protease.
Polygonium tinctorium Leaf
Evaluation of the Bioactivity of Polygonium tinctorium Leaf: Potential Clinical Uses
The leave of Polygonum tinctorium (LPT) have been used for centuries as a traditional medicine and as a food ingredient and natural dye. The aim of the current study was to develop high-value added products using LPT. Hot water extract (HWE) and ethanol extract (EE) of LPT were prepared, respectively, and their bioactivity was evaluated. The extraction ratio for the HWE was 27.6%, which was two-fold higher than that of the EE. The contents of total polyphenol in the HWE and total sugar in the EE were 51.2 mg/g and 297.8 mg/g, respectively. The total flavonoid and reducing sugar contents were similar in the extracts, irrespective of the extraction solvent.
The HWE did not show antimicrobial activity in a disc-diffusion assay, but the EE showed strong growth inhibition against gram-positive bacteria. The EE exhibited stronger DPPH and ABTS radical scavenging activities and reducing power than those of the HWE. The HWE was particularly effective as a scavenger of nitrite ( of ). In an AntiThrombosis activity assay, the EE showed significant antiCoagulation activity as determined by an extended blood Coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time), in addition to platelet aggregation activity. The HWE also showed platelet aggregation inhibitory activity. This report provides the first evidence of AntiThrombosis activities of LPT. Our results suggest that LPT has potential as a new antioxidant and AntiThrombosis agent.
Pueraria lobata(Willd.)Ohwi extract
anti-inflammatory effects of Total Isoflavones from Pueraria lobata on Cerebral ischemia in Rats
Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of earliest and most important edible crude herbs used for various medical purposes in Oriental medicine. The aim of the present study was to determine the anti-inflammatory effects of Total Isoflavones from P. lobata (TIPL), which contains the unique isoflavone puerarin, in ischemia in vivo models. Oral administration of TIPL (100 mg/kg) reduced the brain infarct volume and attenuated ischemia -induced cyclooxygenase-2 (COX-2) up-regulation at 2 days after middle cerebral Artery occlusion (MCAo) in rats.
Moreover, TIPL reduced activation of glial fibrillary acid protein (GFAP) and CD11b antibody (OX-42) at 7 days after MCAo in hippocampal CA1 region. These results show that TIPL can protect the brain from Ischemic Diseases damage after MCAo. Regarding the immunohistochemical study, the effects of TIPL may be attributable to its anti-inflammatory properties by the inhibition of COX-2 expression, astrocyte expression, and microglia.
Ethnopharmacological relevance: Radix Salviae miltiorrhizae (Danshen) and Radix Puerariae lobatae (Gegen) have long been used in traditional Chinese Medicine and serve as the principal herbs in treating Cardiovascular Disease.
Aims of the study: In the present study, an aqueous extract comprising Danshen and Gegen in the ratio of 7:3 (DG) was investigated for its anti-hypertension in vivo and vasodilative activities ex vivo.
Materials and methods: The anti-hypertensive effect of DG extract was investigated in spontaneously hypertensive rat (SHR) by measuring systolic blood pressure (SBP). Oral administration of DG extract was started at age of 6 weeks and 14 weeks for the preventive and therapeutic studies, respectively. blood pressure was measured by tail-cuff method biweekly for 12 weeks. The ex vivo vasodilative activities of DG extract, its dependency on endothelium and the involvement of nitric oxide, prostacyclin and potassium channels were investigated using isolated rat aorta ring in organ bath.
Results: For in vivo study, systolic blood pressure was significantly reduced in DG extract-treated groups (90.2 and 300 mg/kg) as compared with the SHR control in both preventive and therapeutic studies. However, DG extract was unable to suppress or delay the onset of hypertension in the preventive study. For ex vivo study, the results showed that DG extract induced a concentration-dependent relaxation in aorta and persisted response was observed with the removal of endothelium. Besides, pretreatment with a non-selective potassium channel inhibitor tetraethylammonium (TEA) also significantly inhibited DG extract-induced vasodilation. Further investigations on specific potassium channel blockers revealed that ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, inward rectifier potassium (Kir) inhibitor barium chloride and voltage-dependent potassium (Kv) channel inhibitor 4-aminopyridine, but not BKCa channel inhibitor iberiotoxin, exerted significant inhibition on DG extract-induced vasodilation.
Conclusions: The results of in vivo SHR animal model suggested that DG aqueous extract possessed blood pressure lowering effect on both pre- and post-hypertensive rats, which could be explained by its endothelium-independent vasodilation via the opening of KATP, Kir and Kv channels.
Pterocarpus mildbraedii
The study was undertaken to evaluate the in vitro antioxidant, anti-inflammatory and Thrombolytic properties of methanolic extract (PMME) and fractions of the leaf of Pterocarpus mildbraedii with a view to exploring the therapeutic potentials of the plant especially as far as treatment and management of oxidative, inflammatory and Heart related disorders are concerned. The study involved collection, identification, extraction with 80% methanol, fractionation of hydromethanolic extract of P. mildbraedii leaves with n-hexane, ethyl acetate and nbutanol; evaluation of the contents for total phenolics, flavonoids as well as vitamins C and E. Evaluation of the antioxidant and anti-inflammatory potentials of the plant using 2, 2′-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power, hydrogen peroxide reduction, total antioxidant capacity (TAC), and stabilization of erythrocyte membrane and inhibition of albumin denaturation were also carried out.
The total phenolic content ranged between 13.31 ± 0.12 and 234.99 ± 2.64 GAE (gallic acid equivalent)/g, flavonoid content ranged between 44.30 ± 0.74 and 228.74 ± 7.44 QE (quercetin equivalent)/g, vitamin C content was 11.98 ± 0.04 mg/g while vitamin E content was 8.62 ± 0.29 ìg/g. The fractions exhibited potent and significant antioxidant and antiinflammatory activities which are concentration-dependent, as well as appreciable Thrombolytic activities.
Moreover, the extract and fractions compared favourably with various reference drugs used in the study. It was observed that the extract and its fractions possessed bioactive components with beneficial effects in the management of oxidative, inflammatory and Heart -related conditions.
This study obtained hydro-alcoholic extract and different solvent fractions of leaf of P. mildbraedii, evaluated the in vitro antioxidant , anti-inflammatory and Thrombolytic activities of the extract and fractions. It further studied the effect of the fraction and extract on cardiac markers, antioxidant s and haematological parameters in Wistar albino rats. These were with a view to validating the acclaimed cardioprotective and haematopoietic potential of the plant.
Leaves of P. mildbraedii were collected, exhaustively extracted with 80% methanol to yield methanolic extract termed PMME and was successively fractionated using solvent of increasing polarities. The extract and its fractions were phytochemically screened and tested for in vitro antioxidant , anti-inflammatory and Thrombolytic potentials using standard methods. In the cardioprotective study, twenty-five male rats were randomly divided into five groups of five rats each, orally treated with ethyl acetate fraction (EAF) for 21 days and Myocardial Infarction was induced by i.p injection of isoproterenol (ISO) at 85 mg/kg bwt (except the control). The animals were sacrificed for the collection of blood samples and Heart tissue which were used for biochemical and histological examinations. For the haematopoietic study, twenty male rats were randomly divided into four groups of five rats each, and treated with PMME for 14 days.
The rats were sacrificed and blood was collected for haematological examinations. Data collected were subjected to appropriate descriptive and inferential statistical analyses. Phytochemical screening of both extract and fractions revealed the presence of alkaloids, flavonoids and tannins. The extract and fractions possessed and exhibited potent as well as appreciable antioxidant, anti-inflammatory and Thrombolytic activities, with EAF being the most potent. The GC-MS profiling of the PMME and the EAF revealed 113 and 88 chemical compounds, respectively. It was observed that ISO caused a significant (ρ<0.05) increase in the concentration of cTnT (64.96%) and activities of CK-MB (44.18%) and LDH (61.64%) while pre-treatment with EAF significantly (ρ<0.05) decreased the concentration and activities of these biomarkers. Also, a significant increase (22.05%) in plasma total protein level was recorded while the total Heart protein level decreased by 67.95% as a result of the administration of ISO.
However, pre-treatment with EAF prevented the derangements of the total protein levels in both the plasma and Heart . Furthermore, while lipid profile, enzymatic and non-enzymatic antioxidant levels were perturbed in ISO-induced rats, normal levels were maintained in the groups of rats pre-treated with EAF. Histopathological cross-examination of Heart section confirmed Myocardial injuries in ISO-induced rats while pre-treated animals showed lesser degree of damage.
Moreover, the oral administration of PMME caused significant (ρ<0.05) increase in haemoglobin content and PVC while the red cell indices (MCV, MCH and MCHC levels) were not affected. The study concluded that extract and fractions of the P. mildbraedii leaf possessed strong antioxidant, anti-inflammatory and Thrombolytic potentials. The leaf’s EAF exhibited cardioprotective activity against ISO-induced Myocardial Infarction and PMME demonstrated haematopoiesis-enhancing potentials indicating that the plant can be explored in the management of Heart -related and haematopoietic disorders.
The study evaluated the effects of Pterocarpus mildbraedii leaf extracts on Myocardial Infarction induced by isoproterenol (ISO) in Wistar albino rats with a view to ascertain the value of its use in the management of Heart-related Diseases . Fresh plant leaves were collected, identified, extracted, fractionated and the aqueous layer partitioned with ethyl acetate. GC-MS was carried out on the ethyl acetate fraction (EAF) and unknown compounds were identified by comparing measured mass spectral data with those in NIST 14 Mass Spectral Library. Twenty-five adult rats were divided into five groups of 5 rats each.
Groups I &II were the control groups. Rats in groups III-V were pretreated with 50 mg/kg and 100 mg/kg of EAF and 1.8 mg/kg of propranolol respectively for 21 days. Myocardial Infarction was then induced in all the rats (except those in Group I) with the intraperitoneal injection of ISO (85 mg/kg) for 2 days. Afterwards, the rats were sacrificed and blood samples, Heart homogenate and samples for histological studies were aseptically collected.
Activities of cardiac biomarkers, lipid profile, enzymatic and non-enzymatic antioxidant s were evaluated using standard methods. GC-MS analysis showed that the most abundant components of the plant are propionic acid, 2,3-dimethylphenyl ester, catechol, octyl-β-D-glucopyranoside, phenol and n-Hexadecanoic acid. Administration of ISO caused significant elevation of the activities of cardiac biomarkers (troponin-T concentrations, creatine kinase-MB and lactate dehydrogenase) while rats pretreated with EAF had significantly lower levels of the biomarkers.
Moreover, alterations in lipid profile, enzymatic and non-enzymatic antioxidant s brought about by the administration of ISO were ameliorated. Histological examinations revealed lesser degree of Myocardial injury in pre-treated rats.
Rehmanniae Radix extract
Ethnopharmacological relevance: In traditional Chinese medicine (TCM), Rehmanniae Radix (RR, derived from the root of Rehmannia glutinosa (Gaertn.) DC.) is commonly used as natural medicine for thousands of years, two types including the dried and rice-wine processed RR were used for different clinical purposes respectively, which were the typical case that pharmaceutical effect changed by processing in TCM.
Aim of study: The goal of this study was to investigate the differences in the antiThrombosis and hematopoietic effects of extracts of dried and processed RR (DRR and PRR) in vivo, and to explore the chemical basis underlying changes of medicinal properties caused by processing.
Materials and methods: The aqueous extracts of DRR and PRR were prepared. Protective effect of varying doses of different extracts were investigated in type-I carrageenan induced mice tail Thrombosis and cyclophosphamide induced myelosuppression model. The chemical composition of DRR and PRR extracts were determined by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC/Q-TOF-MS).
Results: In antiThrombosis activity tests, PRR possessed less ameliorated effects than DRR in the model mouse on body temperature, tail thrombus length and blood flow . Both DRR and PRR had no significant influence on prothrombin time (PT) and activated partial thromboplastin time (APTT), only high dose DRR could decrease the content of fibrinogen (FIB) in plasma. Histological examination of lung tissue suggested that Thrombosis was significantly improved in DRR-H group. For myelosuppression model, only PRR could improve peripheral hemogram, both DRR and PRR had hematopoietic effects as demonstrated by their abilities to ameliorate the bone marrow nucleated cells (BMNC) and pathology of bone marrow tissue. The hematopoietic effects of PRR were significantly more potent than that of DRR at the concentration of 9 g/kg. By comparing the chemical composition, we found that iridoid glycosides were decreased and furfural derivatives increased in DRR after processing which may be the chemical mechanism contribute to the differences in efficacy.
Conclusions: According to the results of this research, processing with rice wine for nine cycles significantly reduced antithrombotic effects and enhanced the hematopoietic effects of DRR as demonstrated in model mice. It can scientifically explain the different effect among two types of RR in clinical through the diverse method of processing and usage. Meanwhile, the predicted activity compounds from two types of RR can be potential candidates for the treatment of Thrombosis and anemia.
Ethnopharmacological relevance: In traditional Chinese medicine (TCM) and modern pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent anti-thrombotic activity that decreases after processing by nine steaming and drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity of the DRR components, the chemical mechanism leading to efficacy changes of DRR caused by processing is still unclear.
Aim of study: This study aimed to trace the anti-thrombotic active compounds of DRR and different degrees of processed RR (PRR) and to evaluate the synergistic effects among different active components.
Materials and methods: The anti-thrombotic active chemical fraction of DRR extracts was evaluated. Targeted fractions of the processed products of RR were prepared at different processing stages. The changes in monosaccharides, oligosaccharides and secondary metabolites during processing were characterized by multidimensional high-performance liquid chromatography (HPLC). The anti-thrombotic effects of targeted fractions of different RR samples were evaluated by analyzing the length of tail thrombus (LT) and serum biochemical indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect relationships were investigated by partial least squares regression (PLSR) analysis and gray correlation analysis (GRA). Finally, the active compounds were screened by spectrum-effect relationship analysis and validated in vivo, and their synergistic effects were determined by Webb’s fraction multiplication method.
Results: Six ingredients highly associated with anti-thrombotic activities were screened out by the spectrum-effect relationship analysis, of which oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides (catalpol, leonuride and melitoside) possessed a synergistic effect on tumor necrosis factors (TNF-α), interleukin 1β (IL-1β) and plasminogen activator inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with synergistic coefficient (SC) > 1.
Conclusion: The main material basis of the anti-thrombotic activities of DRR is oligosaccharide components of stachyose, raffinose and sucrose, iridoid glycosides components of catalpol, leonuride and melittoside. The two kinds of components exert synergistic anti-thrombotic effects by inhibiting the expression of inflammatory factors and regulating the balance of the fibrinolysis system.
Anti-Thrombic activity of Korean herbal medicine, Dae-Jo-Whan and its herbs
The anti-Thrombic properties of the Korean herbal medicine, Dae-Jo-Hwan (DJW), which is consisted of 11 herbs (indicated as concentrations) of Rehmanniae radix 24%, Hominis placenta 5%, Testudinis carapax 9%, Eucommiae cortex 9%, Asparagi radix 9%, Phellodendri cortex 9%, Achyranthis radix 7%, Liriopis tuber 7%, Angelicae sinensis radix 7%, Ginseng radix 6%, and Schizandrae fructus 3%, were investigated. The extracts of DJW and its 11 herbs, except G. radix, A. sinensis radix and S. Fructus, inhibited the endotoxin-induced hepatic Venous Thrombosis in high cholesterol diet-treated rats. Also the extract inhibited the endotoxin-induced decrease in blood platelet s and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats.
In in vitro experiments, the extract was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin -induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. In conclusion, the protection of extracts of Korean herbs on the Ischemic Diseases Infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and Thrombic action.
Rutin
Rutin- potent natural Thrombolytic agent
Thrombosis, the formation of blood clot s, is a cause not only of Heart attacks and strokes, but of Deep Venous Thrombosis (DVT) and Pulmonary Embolism as well. The number one killer of Americans is a blood clot that blocks blood flow to the Heart or to the brain and approximately half of all morbidity and mortality in the United States can be attributed to Heart attack or Stroke. All the blood clot related conditions are life-threatening, and so there is a need for safe, effective and preventive treatment. A natural substance rutin, also called rutoside, is a citrus flavonoid glycoside found in Fagopyrum esculentum (buckwheat), the leaves and petioles of Rheum species, and Asparagus. This flavonoid compound has shown effective Thrombolytic activity (prevents the formation of blood clots) by blocking the enzyme protein disulfide isomerase (PDI) found in all cells involved in blood clotting. Food and Drug Administration (FDA) has established that rutin is safe and, thus provides a safe and inexpensive drug that could reduce recurrent clots and help save thousands of lives.
Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille
Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and Anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clotting in concentration dependent manner.
Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin ) induced acute thromboEmbolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for Cardiovascular Diseases.
Salvia miltiorrhiza Bge.root extract
Chemistry and Biological Activities of Caffeic Acid Derivatives from Salvia miltiorrhiza
Caffeic acid (3,4-dihydroxycinnamic acid), one of the most common phenolic acids, frequently occurs in fruits, grains and dietary supplements for human consumption as simple esters with quinic acid or saccharides, and are also found in traditional Chinese herbs.
Caffeic acid derivatives occur as major water-soluble components of Salvia miltiorrhiza, including caffeic acid monomers and a wide variety of oligomers. This review provides up-to-date coverage of this class of phenolic acids in regard to structural classification, natural resources, chemical and biosyntheses, analytical methods and biological activities including antioxidant , anti-ischemia reperfusion, anti-Thrombosis , antihypertension , anti-fibrosis, antivirus and antitumor properties . Special attention is paid to both structural classification and biological activities. The structural diversity and the pronounced biological activities encountered in the caffeic acid derivatives of S. miltiorrhiza indicate that this class of compounds is worthy of further studies that may lead to new drug discovery.
Over the past 100 years, Salvia miltiorrhiza f. alba (Lamiaceae) (RSMA) roots have been used to cure thromboangiitis obliterans (TAO) in local clinics. This study aimed to confirm the anti-thrombotic efficacy of 12 phenolic acids obtained from RSMA and to clarify the possible underlying mechanisms. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) experiments demonstrated that most of the phenolic acids markedly inhibited PAI-1 protein and mRNA levels but increased t-PA protein and mRNA levels in TNF-α-induced EA.hy926 cells (P < 0.05 or 0.001), with lithospermic acid displaying the strongest effect.
In vitro antiCoagulation and antiplatelet aggregation assays showed that lithospermic acid and salvianolic acid B significantly prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), decreased fibrinogen concentration (FIB), and inhibited platelet aggregation induced by adenosine diphosphate (ADP) in rat blood. Both lithospermic acid and salvianolic acid B markedly down-regulated the expression of factor Xa and factor IIa on the external surface of EA.hy926 cells and demonstrated significant anti-factor IIa and anti-factor Xa activity using chromogenic substrates in vitro. Western blot results revealed that both lithospermic acid and salvianolic acid B also significantly inhibited the expression of TF, p-p65, p-p38, and pJNK proteins induced by TNF-α.
These results indicated that all of the phenolic acids appeared to have some anti-thrombotic activity, with salvianolic acid B and lithospermic acid markedly decreasing the chance of Thrombosis by regulating the NF-κB/JNK/p38 MAPK signaling pathway in response to TNF-α.
Anti-Thrombolytic effect of Salvia miltiorrhiza Bge extract in rats
Purpose: To study the effects of Salvia miltiorrhiza Bge. extract (SMBE) on Thrombosis in rats.
Methods: SMBE was obtained in water at 60 oC in an oven and then freeze-drying. Rats were divided into 6 groups of ten rats each: normal group, control group, reference group (aspirin 5 mg/kg) as well as three groups of SMBE groups (25, 50 and 100 mg/kg doses). Treatments were given orally once daily for 14 days. Common carotid Artery FeCl3-induced thrombus and inferior vena cava Thrombosis occlusion time, plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandine F1α (6- keto-PGF1α) were measured in the rats.
Results: Compared with control group, all doses of SMBE significantly and dose-dependently prolonged Thrombosis occlusion time, reduced the weight of thrombus and increased the inhibition rate of thrombus (p < 0.01). Plasma TXB2 concentration of all SMBE groups decreased dose-dependently (p < 0.05) while that of 6-keto-PGF1α increased with decrease in extract dose (p < 0.05). There was association between 6-keto-PGF1α/TXB2 and Arterial or Venous thrombus weight for all treatments, and also with occlusion time for SMBE treatment, but not for aspirin.
Conclusion: The results demonstrate the AntiThrombosis effect of SMBE in rats. This finding suggests that the plant is a potential therapy for Thrombosis.
Research advances in antiplatelet activation of water soluble compounds in Salvia miltiorrhiza
Platelet s are fragments of cytoplasm that are released from the mature megakaryocyte of the bone marrow.The main function of platelets is Coagulation and hemostasis.platelet s play a central role in formation of pathological Thrombosis. Many Ischemic Diseases Diseases are caused by excessive activa-tion of platelets, which can lead to Thrombosis and death. Salvia miltiorrhiza Bunge, the dry roots and rhizomes of the Salvia miltiorrhiza plants,includes some water-soluble compounds,which play positive effects on diverse Diseases such as neurodegenerative Diseases , diabetic complications or cardiovas-cular Diseases .In this paper,the components of the water-soluble in Salvia miltiorrhiza,as well as the applications in thrombotic Diseases are summarized. The results show that water-soluble compounds include salvianolic acid A,salvianolic acid B,protocatechuic aldehyde, Danshensu, etc. The water-soluble compounds are applied to Ischemic Diseases Stroke, Myocardial Infarction and other Diseases caused by thrombus.
We also discussed the mechanisms of water-soluble compounds on the platelet s based on our research results and the data obtained from references. The results indicate that water soluble compounds in Salvia miltiorrhiza play the antiplatelet and antithrombotic effects via different mechanisms, for example, salvianolic acid A inhibits platelet aggregation without promoting bleeding by increasing cAMP, inhibiting phosphoinositide 3-kinase (PI3K) and affecting GPCRs (G protein-coupled receptors) signaling path-ways; salvianolic acid B inhibit platelet s as a P2Y12 antagonist and PDE inhibitor; Danshensu inhibits platelet activity may be related to inhibition of calcium influx.In conclusion,thrombotic Diseases seriously affect human life and health. The existing antiplatelet drugs have some disadvantages.
For example, aspirin may cause intracranial hemorrhage, and clopidogrel may play a slower role. Salvia miltiorrhiza as a traditional Chinese medicine has positive pharmacological activity and exerts anti-platelet aggrega-tion through different mechanisms.In the future,we will develop the new drugs which prevent and treat thrombotic Diseases with the further study of the pharmacological effects and mechanisms of Salvia miltiorrhiza.
Background: Salvia miltiorrhiza (Danshen, DS) and Panax notoginseng (Sanqi, SQ) are famous traditional Chinese herbs, and their herbal pair (DS–SQ) has been popular used as anti-thrombotic medicines. However, there is still a lack of sufficient scientific evidence to illustrate the optimum combination ratio of these two herbs as well as its action mechanisms. The purpose of this study is to investigate the anti-thrombotic effects of DS–SQ on zebrafish and explore its possible action mechanism.
Methods: Firstly, the chemical components in DS–SQ extract were analyzed by LC–ESI–MS/MS. Then, a phenylhydrazine (PHZ)-induced zebrafish Thrombosis model was developed for evaluating the anti-thrombotic effects of DS–SQ extracts with different combination ratios and their nine pure compounds. Followed, Real-time quantitative PCR (RT-qPCR) assays were performed to investigate the potential antithrombotic mechanisms of DS–SQ.
Results: Thirty-three components were tentatively identified by LC–MS analysis. DS–SQ at the ratio of 10:1 presented the best anti-thrombotic effect, and rosmarinic acid, lithospermic acid and salvianolic acid B of DS showed good anti-thrombotic activity on zebrafish Thrombosis model. The RT-qPCR assays indicated that DS–SQ (10:1) could cure the PHZ-induced Thrombosis by downregulating the expression of PKCα, PKCβ, fga, fgb, fgg and vWF in zebrafish.
Conclusions: DS–SQ with the combination ratio of 10:1 showed optimum anti-thrombotic effect on PHZ-induced zebrafish Thrombosis model, which provided a reference for reasonable clinical applications of DS–SQ herbal pair.
Sargentodoxa cuneata (Oliv.) Rehd. et Wils. extract
Purpose: To investigate the anti-Thrombosis and anti-tumor effect of the water extract of the caulis of Sargentodoxa cuneata (Oliv.) Rehd. et Wils. (WCSW) in rat and mouse models.
Methods: WCSW extract was prepared and the main constituents were determined by high pressure liquid chromatography (HPLC). The acute toxicity of the extract was determined in mice. platelet aggregation in rat platelet -rich plasma (PRP) was examined to evaluate the effect of the extract on platelet function. Thereafter, the cytotoxic activity of WCSW on HL60, A549, S180 and H22 cells was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo antitumor effect of WCSW was further evaluated on H22 cells transplanted in mice, while the expression of caspase-3, caspase-9, Bcl-2 and Bax proteins were assayed by Western blot analysis.
Results: Protocatechuic acid, rhodiola glucoside and chlorogenic acid were identified as the main constituents of WCSW. platelet aggregation was significantly inhibited by treatment with the extract at concentrations of 1, 5 and 10 mg/mL. WCSW also showed significant inhibitory effect on HL60, A549, S180 and H22 cells in vitro with half maximal inhibitory concentration (IC50 value of 321.9, 285.0, 130.3 and 76.1 μg/mL, respectively. Furthermore, WCSW exhibited obvious anti-tumor effect on H22 transplanted tumor in vivo. After treatment with WCSW, caspase-3, caspase-9 and Bax were significantly (p < 0.05) up-regulated, whereas Bcl-2 was significantly (p < 0.05) down-regulated in the tumor tissues.
Conclusion: WCSW possesses significant antiThrombosis and anti-tumor effect, and therefore, has the potentials to be developed into effective drugs for clinical treatment of cancer and Thrombosis Diseases.
Sophora japonicaL. extract
anti-platelet effects of flavonoids and flavonoid-glycosides from Sophora japonica
A methanol extract of Sophora japonica was subjected to anti-platelet activity guided fractionation affording the isolation of four flavonoids and six flavonoid-glycosides: biochanin A (1), irisolidone (2), genistein (3), sissotrin (4), sophorabioside (5), genistin (6), tectoridin (7), apigenin (8), quercitrin (9), and rutin (10).
The structure of each compound was determined by a variety of spectroscopic methods. Among the compounds, 1, 3, and 7 showed ∼2.5–6.5 fold greater inhibitory effects on arachidonic acid (AA) and U46619 induced platelet aggregation (IC50: 19.9 and 99.8 μM; 20.3 and 53.8 μM; 25.9 and 123.4 μM, respectively) than acetylsalicylic acid (ASA, IC50: 63.0 and 350.0 μM). Compound 2 was an ∼22–40 fold stronger inhibitor than ASA on AA and U46619 induced aggregation (IC50: 1.6 and 15.6 μM, respectively).
Spirulin (Arthrospira platensis)
antithrombotic properties of Spirulina extracts against platelet-activating factor and thrombin
Spirulina (Arthrospira maxima) components have shown several health-benefits, including immunomodulatory and anti-inflammatory properties . Even though a few studies have examined the effects of some Spirulina-derived ingredients on platelets, none studied the effects on platelet aggregation induced by inflammatory and thrombotic mediators, namely platelet activating actor (PAF) and thrombin . In the present study, the antithrombotic properties of compounds extracted from Spirulina, namely phycocyanobilin (PCB), phycocyanin-protein, polysaccharides (PS) and lipid extracts, but also of bioactive HPLC-separated lipid-fractions, were assessed in washed rabbit platelet s (WRP) activated by PAF and thrombin.
All extracts showed strong anti-PAF and anti-thrombin activities in WRP. PCB showed the strongest inhibitory effects on PAF/thrombin -induced platelet aggregation, with a stronger anti-thrombin effect, followed by the relative strong anti-PAF inhibitory effects of the total lipid extracts. HPLC-separation of Spirulina lipid extracts into lipid subclasses’ fractions showed that specific polar lipid fractions of glyco-lipids and PAF-like phosphatidylcholine moieties exhibited the strongest anti-PAF effects. Some of these lipid-fractions and PCB, when assessed at higher concentrations on WRP showed also an anti-PAF agonistic effect, with the PS extract exhibiting the strongest platelet-aggregatory effect.
In conclusion, the results suggested that Spirulina seems to be a sustainable source of bioactive compounds with strong anti-PAF and anti-thrombin properties, and thus a potential candidate for developing food supplements and nutraceuticals against inflammation, Thrombosis and related disorders. However, more studies are needed to explore the potential and safety of further use of Spirulina.
Spirulan from Blue-Green Algae Inhibits Fibrin and blood Clots: Its Potent antithrombotic effects
We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties . Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins.
In vitro assays using human fibrin and mouse blood Clot s showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3)-induced carotid Arterial thrombus model and collagen and epinephrine-induced Pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for Thrombosis -related Diseases .
Stevia rebaudiana
Background and Aim: The antioxidant, antidiabetic, antiamnesic, cytotoxic, Thrombolytic and biofilm inhibition activities of seven fractions (methanol, ethanol, ethyl acetate, n-hexane, n-butanol, chloroform and aqueous) of Stevia rebaudiana leaves were determined.
Methodology: The antioxidant contents and activity was measured as total phenolic contents (TPC), total flavonoid contents (TFC) and free radical scavenging assays. Anti-diabetic and antiamnesic efficacies were tested in terms of glycation, alpha amylase and acetylcho-linesterase inhibition s. DNA damage protection and hemolysis analysis were done to evaluate cytotoxicity. In addition Thrombolytic and antibiofilm studies were performed by prescribed methods.
Results: The n-butanol fraction had highest TPC, whereas, optimal TFC and antioxidant activity were observed in methanol fraction. Ethyl acetate, aqueous and chloroform fractions showed maximum antiglycation, alpha amylase inhibitory and acetylcholinesterase inhibitory activities respectively. In cytotoxic profile, hemolytic activity was in the range of 4-47%, with n-butanol being the most potent hemolytic agent. All fractions prevented DNA damage except ethanol, n-butanol and aqueous fractions. The greatest biofilm inhibition was produced by n-hexane extract for Pasteurella multocida strain and aqueous fraction for Staphylococcus aureus strain. Highest (27%) Thrombolytic activity was studied in n-hexane sample.
Conclusion: The current study highlighted significant antioxidant, antidiabetic, antiamnesic, cytotoxic, Thrombolytic and antibiofilm activities of Stevia rebaudiana leaves that might be significant for the management and treatment of various Diseases.
Taxillus chinensis (DC.) Danser extract
Ethnopharmacological relevance: Zihuai recipe (ZHR), a Chinese herbal prescription, is widely used for the clinical treatment of Diminished ovarian reserve (DOR) infertility. However, little is known regarding its underlying mechanisms of DOR treatment.
Aim of the study: This study aimed to investigate the beneficial effects of ZHR on the treatment of DOR and to reveal the underlying mechanisms.
Materials and methods: Sixty 8-week-old Sprague–Dawley female rats were randomly divided into the following six groups (n=10 per group): control group, DOR group, low-dose (2.7 g/kg/day) ZHR (L-ZHR) group, medium-dose (5.4 g/kg/day) ZHR (M-ZHR) group, high-dose (10.8 g/kg/day) ZHR (H-ZHR) group, and hormone replacement therapy (HRT) group. The DOR model was established in all the groups, except the control group, by a single intraperitoneal injection of 90 mg/kg cyclophosphamide (CTX). After the induction of the DOR model, rats were weighed and administered either the relevant dose of ZHR or an equal volume of saline solution (in the control and DOR groups). Rats in the HRT group received estradiol valerate tablets (0.16 mg/kg/day) for 4 days， with medroxyprogesterone acetate tablets (0.86 mg/kg/day) added on day 4. After 32 days of treatment, the rats were euthanized and the ovaries were collected for sampling. Ovarian morphology was observed by hematoxylin and eosin staining and the number of follicles was counted under a microscope. The serum levels of anti-Müllerian hormone (AMH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were quantified by ELISA. A TUNEL assay was used to analyze the level of apoptosis of the ovarian cells. The protein expressions of p-PI3K, p-AKT, PI3K, AKT, cleaved caspase-3, BAX, and Bcl-2 were measured by western blotting and immunohistochemistry. Data analysis was performed with SPSS 20.0 software.
Results: ZHR administration increased the ovarian index and the serum levels of AMH, GnRH, and E2, while it lowered those of FSH and LH. ZHR treatment also increased the numbers of primordial, primary, secondary, and antral follicles, as well as the numbers of corpora lutea, but decreased the number of atretic follicles. Furthermore, ZHR administration decreased the percentage of TUNEL-positive ovarian cells. After treatment with ZHR, the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, cleaved caspase-3 and BAX were decreased, whereas the level of Bcl-2 was increased.
Conclusions: ZHR improved the ovarian reserve in CTX-induced DOR rats. The mechanisms of ZHR on DOR may be mediated through the regulation of gonadal hormones of the hypothalamic-pituitary-ovarian axis, and the inhibition of PI3K/AKT-mediated apoptosis in granulosa cells.
Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening Disease , SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (lóng dǎn; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma (shān yào; the tuber of Dioscorea batatas), Cassiae Semen (jué míng zǐ; the dried seed of Cassia tora) and Loranthi Ramus (sāng jì shēng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii (gǒu jǐ; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50) and 50% of viral replication (EC50) were determined.
The resulting selective index values (SI = CC50/EC50) of the most effective extracts CBE, GSH, DBM, CTH and TCH were > 59.4, > 57.5, > 62.1, > 59.4, and > 92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39 μg/ml and 44 μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics.
The outbreak of Covid -19 Disease caused by SARS-CoV-19, along with the lack of targeted medicaments and vaccines, forced the scientific world to search for new antiviral formulations. In this review, we describe the current knowledge about plant extracts containing polyphenols that inhibit Covid -19.
Many plant-derived natural compounds (polyphenols) might provide a starting point for the research on the use of plant extracts in coronavirus treatment and prevention. Antivirus polyphenolic drugs can inhibit coronavirus enzymes, which are essential for virus replication and infection. This group of natural substances (betulinic acid, indigo, aloeemodine, luteolin, and quinomethyl triterpenoids, quercitin or gallates) is a potential key to designing antiviral therapies for inhibiting viral proteases.
The known pharmacophore structures of bioactive substances can be useful in the elaboration of new anti-Covid -19 formulations. The benefit of using preparations containing phytochemicals is their high safety for patients and no side effects.
Tetracera sarmentosa
Background: The plant under investigation (Tetracera sarmentosa) is a dicotyledonous flow ering plant and belongs to the family Dilleniaceae. The goal of our investigation was to determine whether the leaf extracts of this plant held any significant medicinal properties .
Methods: Leaves of T. sarmentosa were extracted with pure ethanol (EETS) and methanol (METS), and then methanol extract fractioned with n-hexane (NHFMETS) and chloroform (CHFMETS). The extracts and fractions were tested for antioxidant activity, which was measured by using qualitative and quantitative procedures. Thrombolytic activity was evaluated by the Clotlysis test. Analgesic activity was evaluated employing the acidic acid-induced writhing test, the formalin-induced paw licking test and tail immersion on Swiss albino mice. The anti-inflammatory activity test was studied using the paw edema test. Forced swimming, tail suspension, elevated plus maze and hole board model tests were used to evaluate neuropharmacological activity.
Results: All the extracts and fractions possessed antioxidant effects. All the extracts, fractions and streptokinase exhibited significant (p<0.0001) Clotlysis. The extracts and fractions produced significant analgesic effects as evaluated by the acetic acid writhing test, the formalin-induced paw licking test and the tail immersion method. Similarly, carrageenan-induced inflammation was significantly antagonized by the treatments. The extracts and fractions also significantly showed neuropharmacological (antidepressant and anxiolytic) effects.
Conclusions: The overall results suggested that this plant deserves further investigation to isolate the active compounds which are responsible for these activities and to establish the mechanism of action.
Typha angusti foliaL extract
Objective: The aim of this study was to investigate the in vitro Thrombolytic activity and cytotoxicity of T angustifolia leaf extract.
Methods: An in vitro Thrombolytic model was used to evaluate the Clotlysis effect of different extracts of T.angustifolia Linn along with Streptokinase as a positive control and distilled water as a negative control. The cytotoxic activity of diffetent extracts of T.angustifolia leaves was evaluated by Brine Shrimp Lethality Bioassay.
Results: An in vitro Thrombolytic model of aqueous, methanol and chloroform extracts have shown 51.76±2.5%, 58±2.32 and 18±1.84 Clotlysis respectively, where as the positive control Streptokinase shown 79.6±1.10 and negative control shown negligible 2.44±0.62. The aqueous, methanol and chloroform extracts have shown brine shrimp lethality with LC50 value of 40μg/ml, 30μg and 104 μg/ml respectively. It was found that aqueous and methanol extracts of T angustifolia possesses potential Thrombolytic activity as well as cytotoxicity.
Conclusion: The present investigation revealed that the aqueous and methanol extracts of T angustifolia possesses Thrombolytic properties as well as cytotoxicity effects and it can be further used for treatment of Cardiovascular Diseases and cancer
In Vitro Thrombolytic and antibacterial properties
of Typha angustifolia Fibre extracts
Objective: The aim of this study was to investigate the antibacterial activity and in vitro anti-Thrombolytic activity of Typha angustifolia fibre extracts.
Methods: The Thrombolytic activity was screened by in-vitro Clotlysis model. In this model the blood sample (500μl/tube) from human volunteer has been collected in micro centrifuge tubes. After incubation the standard drug and different dilutions of test drug were added whereas water is taken as control. Percentage of Clotlysis was calculated on the basis of the weight difference of micro centrifuge tubes obtained before and after Clotlysis. The antibacterial properties were determined by agar well diffusion method against S. aureus, B. subtilis, K. pneumoniae, E. coli, P. aerugenosa.
Result: Solvent extracts of T. angustifolia significance Clotlysis activity with reference of Streptokinase as standard. Ethanol and Acetone showed strong antibacterial activity against S. aureus, E. coli and P. aerugenosa (18mm), Methanol showed moderate antibacterial activity against S. aureus, B. subtilis and P. aerugenosa (17mm). Aqueous solution showed antibacterial activity against B. subtilis, P. aerugenosa, S. aureous, E. coli (16mm). Acetone showed moderate antibacterial activity against K.pneumoniae. Ethanol and Methanol showed mild antibacterial activity against K. pneumonia and E. coli (15mm). Aqueous solution showed mild antibacterial activity against K. pneumonia.
Conclusion: The present investigation revealed that Typha angustifolia fibre extracts Possesses positive Thrombolytic properties that could lysis blood Clots. Further studies using in vivo models are required to carry out and establish the effectiveness and pharmacological rationale for the use of Typha angustifolia fibre extracts as a Thrombolytic drug ethanol and acetone extract of T. angustifolia possess strong anti-bacterial activity against bacterial pathogen.
Vitamin B6
Objectives: Individuals with inflammatory bowel Disease (IBD) are at increased risk for Thrombosis and vitamin deficiencies. Low plasma levels of vitamin B6 are an independent risk factor for Thrombosis and may cause hyperhomocysteinemia, another recognized risk factor for Thrombosis. The aim of this study was to evaluate vitamin B6 plasma levels in IBD patients.
Methods: We studied 61 IBD patients: 32 with Crohn’s Disease and 29 with ulcerative colitis. For each patient, three sex- and age-matched healthy control subjects were studied.
Results: Median vitamin B6 levels were significantly lower in IBD patients (22.0 pmol/L, range 3.6–231.0) than in controls (31.1 pmol/L, 3.7–363.4; p < 0.01). In all, 13.1% IBD patients and 5.5% controls had plasma vitamin B6 levels lower than the 5th percentile of distribution in normal controls (p < 0.05). Low vitamin B6 levels were significantly more frequent in patients with active Disease than in patients with quiescent Disease (seven of 26, 26.9%, vs one of 35, 2.9%; p < 0.001). Moreover, patients with active Disease had significantly lower median vitamin B6 levels (13.4 pmol/L, range 3.6–124.0) than patients in a quiescent phase (27.0 pmol/L, 7.8–231.0; p < 0.001). Low vitamin B6 levels were significantly correlated with serum concentrations of C-reactive protein (r = −0.36, 95% CI = −0.59 to −0.09, p < 0.01) and α1-acid-glycoprotein (r = −0.37, 95% CI = −0.59 to −0.10, p < 0.01). Hyperhomocysteinemia was more frequent in patients with low vitamin B6 levels (three of eight, 37.5%) than in patients with normal levels (nine of 53, 17.0%; p = 0.18). There was no statistically significant correlation between vitamin B6 and homocysteine plasma levels (r = −0.13, 95% CI = −0.37 to +0.14, p = 0.33).
Conclusions: Low vitamin B6 plasma levels, an independent risk factor for Thrombosis, are frequent in patients with IBD, especially those with active Disease.
Study on relationships among Deep vein Thrombosis , homocysteine & related B group vitamins
Objectives: Hyperhomocysteinemia has been considered as a potential risk factor for Deep Venous Thrombosis (DVT) but it is still controversy. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with DVT. Our second objective was to document the prevalence of folate, Vitamin B6, and Vitamin B12 level in this patient population.
Methods: Sixty patients with DVT aged from 23 to 84 years, were assessed regarding demographic characteristics, serum levels of homocysteine, folate, vitamin B12, and vitamin B6. The diagnosis of DVT was based upon Wells scoring system and serum D-dimer level and confirmed by Deep Venous Doppler ultrasonography of the lower limbs.
Results: Mean serum homocysteine levels were found significantly higher in patients over the age of 40 years (10.81±4.26 µmol/L vs 9.13±3.23 µmol/L). Of all the patients, 9 patients had homocysteine level above the 15µmol/L, 26 had folic acid level below 3 ng/ml, one had vitamin B12 level below 150 pmol/L, and two had vitamin B6 level below 30 nmol/L. In the hyperhomocysteinemic group, five patients had low folic acid level, one had low vitamin B12 level, and two had low vitamin B6 level.
Conclusions: Hyperhomocysteinemia, in women older than 40 years, may be a risk factor for DVT. Folic acid deficiency may also influence serum homocysteine concentrations. Folate therapy may be offered to the patients with DVT. However further studies are required to clarify the underlying molecular mechanisms.
Poor vitamin B6 status: A novel potential thrombotic factor in chronic obstructive Pulmonary diseas
Vitamin B6 participates as a coenzyme to >100 reactions and is required for the degradation of homocysteine, a strong predictor of atherothrombotic events. Low circulating vitamin B6, however, predisposes to Arterial and Venous Thrombosis, independently of hyperhomocysteinaemia.
Populations studies suggest an intriguing link between low vitamin B6 and systemic chronic inflammation, presumably because vitamin B6 is consumed during inflammation. Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting systemic inflammatory illness and confers an independent higher risk of atherothrombotic events.
While investigating hyperhomocysteinaemia in COPD, we have described for the first time lower vitamin B6 plasma concentrations in COPD patients than in matched controls. We have now re-analyzed our study sample to determine the mechanisms accounting for this COPD-related poor vitamin B6 status.
Willow Bark
Objective: To investigate the efficacy and safety of a standardized willow bark extract in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
Methods: We studied 127 outpatients with hip or knee OA and a WOMAC pain score of at least 30 mm and 26 outpatients with active RA in 2 randomized, controlled, double-blind trials with followup for 6 weeks. OA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg of salicin/day, diclofenac 100 mg/day, or placebo (n = 43, 43, and 41, respectively). Main outcome measure was the pain subscore of the WOMAC OA Index. RA trial: Patients were randomized to receive willow bark extract, corresponding to 240 mg salicin/day (n = 13) or placebo (n = 13). Main outcome measure was the patient’s assessment of pain rated on a 100 mm visual analog scale (VAS).
Results: OA trial: WOMAC pain scores decreased by 8 mm (17%) in the willow bark group and by 23 mm (47%) in the diclofenac group, compared with 5 mm (10%) in the placebo group. The difference between willow bark extract and placebo was not statistically significant (-2.8 mm; 95% CI -12.1 to 6.4 mm; p = 0.55, ANCOVA), but the difference between diclofenac and placebo was highly significant (-18.0 mm; 95% CI -27.2 to -8.8 mm; p = 0.0002, ANCOVA). RA trial: The mean reduction of pain on the VAS was -8 mm (15%) in the willow bark group compared with -2 mm (4%) in the placebo group. The difference was not statistically significant (estimated difference -0.8 mm; 95% CI -20.9 to 19.3 mm; p = 0.93, ANCOVA).
Conclusion: The OA study suggested that the willow bark extract showed no relevant efficacy in patients with OA. Similarly, the RA trial did not indicate efficacy of this extract in patients with RA.
effects OF WILLOW BARK Salix alba AND ITS SALICYLATES ON blood coagulant
The herb white willow Salix alba , also known as willow bark, is used to treat pain and fever. White willow contains a substance salicine that is converted by the body into a salicylate similar to the blood-thinner aspirin. Over the last twenty years, yet another use for aspirin has emerged connected with the discovery of its anti-thrombotic action.
effects OF WILLOW BARK Salix alba AND ITS SALICYLATES ON blood coagulant
The herb white willow Salix alba , also known as willow bark, is used to treat pain and fever. White willow contains a substance salicine that is converted by the body into a salicylate similar to the blood-thinner aspirin. Over the last twenty years, yet another use for aspirin has emerged connected with the discovery of its anti-thrombotic action.
Formulation and Evaluation of Salix alba Herbs Tablet for Post-Covid complication related to blood Clots
Herbal formulations have growing demand in the world market. The present study was designed as formulation and evaluation of salix alba herbal tablet prepared. Tablet was prepared by direct compression method. The present communication also deals with the evaluation of formulated tablets (weight variation, friability, hardness and disintegration time. Salix alba contains a substance (salicine) that is converted by the body into a salicylate similar to the blood-thinner aspirin. Salix alba have anti- thrombotic action which can be use in Post Covid complication related to blood Clot in place of aspirin.
| Size | 50g, 100g, 300g |
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3 reviews for THROMBOLYTIC : Blood Clot Destroyer 200:1
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Rich Ryan –
Another excellent blend!
10 minutes after taking Throm, I noticed a calmness descend upon me. It wasn’t sleepiness, it felt like a focused calm, as my body entered into a deep relaxed healing state. 20-30 minutes after, I noticed my heart was beating more deeply. A stronger more sustained heartbeat. It felt like my blood was flowing more vigorously. I’ve also noticed a healthy blood pressure drop with Throm. I could tell that my entire cardiovascular system was healing.
I used to occasionally have heart palpitations. After using Throm for a week or so, no more heart palps. I can’t remember having even one.
I think this blend will be very important in helping people recover from all of the “heart and blood clot” centric health disasters recently…
It might be a life and death choice for some.
Definitely a must-have.
Good stuff!
Dylan Cobb –
THROM review:
This blend is an absolute game changer. After taking for the first time, I immediately felt like my blood circulation was smoother and quicker. In addition, it appeared to have increased the effects of any blend I was taking with it (possibly as a result of the increased blood flow throughout the body circulating the active properties of the blends). I was surprised that it only took a minute dose to produce such profound effects that lasted for hours! Couple that with the fact that anything I took with it was enhanced as well!
Throm works great for lowing blood pressure as well, and this effect is also practically immediate. I noticed greater mental clarity and performance as another side benefit that I partially credit to the improvement of blood circulation to the brain. Wounds heal much faster as a result of the increased blood flow to injured regions of the body. When it came to sore muscles or achy joints, Throm can address those issues far beyond what you would expect!
I do not have any atherosclerosis or blood clots and I still benefited immensely from this blend in many different ways. If it worked this well for me, I can only image the impact it would have on those who are suffering from atherosclerosis or blood clots! This blend could possibly be the prevention many people need from dying of these ailments. I do not doubt for a second that there are multitudes of people who would not have died of these things if they had been taking THROM!
Jeremiah Holguín –
THROM
I respectfully preface that I am a real person and if you join the telegram group I will talk to you ad-nauseam about these products: I stand by the honor of my very word. 11 months ago I nearly died. I experienced brutal chemical exposure that almost killed me and completely bricked my neurological, cardiovascular, hormonal systems, REM shot immediately that effect alone nearly drove me crazy it took the fullest extent of my knowledge base as a regenerative medicine consultant to keep myself alive. Long story short I got a chance to really test the full gambit of interstellar products which I had already been using for about a year and a half prior: as close to 22/2 as often as possible / 88/8 on a fairly regular basis.
The turgidity of water based systems sets the cardiovascular prescience for how well your body’s hydrological cycle works as a whole. Blood viscosity and pressure are modulated by hermetic impacts in our daily life and by keeping the pipes clear you’ll be able to maximize your dynamic adaptive responses that arise in life’s dynamic moment-to-moment & day-to-day experiences – everything has an impact and something’s hit much deeper and cause more corrosion, and subsequent build up than others. The data deep dive on this is awesome if you’re also into civil and technical engineering like me; think about it: Without plumbing how would our society function? This is maintenance of the flow to your bodies plumbing. be sure to be cognoscent of the effects of excessive blood thinning. It can be hermetic stress in and of itself. Be mindful of how certain foods can effect this like Omega-3’s or how it could modulate chronic IL-6/IL-8 levels… the vocabulary is important if you really want to understand how important this blend is.
I like to pair with EKG + ALZ + PARASLAYER occasionally as I live in the tropics