Antiplatelet Effects of Flavonoids Mediated by Inhibition of Arachidonic Acid Based Pathway (original) (raw)
Related papers
Inhibition of platelet aggregation by some flavonoids
1991
The inhibitory effects of five flavonoids on the aggregation and secretion of platelets were studied. These flavonoids inhibited markedly platelet aggregation and ATP release of rabbit platelets induced by arachidonic acid or collagen, and slightly those by platelet-activating factor. ADP-induced platelet aggregation was also suppressed by myricetin, fisetin and quercetin. The IC50 on arachidonic acid-induced platelet aggregation was: fisetin, 22 microM; kaempferol, 20 microM; quercetin, 13 microM; morin, 150 microM less than IC50 less than 300 microM. The thromboxane B2 formations were also inhibited by flavonoids in platelets challenged with arachidonic acid. Fisetin, kaempferol, morin and quercetin antagonized the aggregation of washed platelets induced by U46619, a thromboxane A2/prostaglandin endoperoxides mimetic receptor agonist. In human platelet-rich plasma, quercetin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine or ADP. These results demonstrate that the major antiplatelet effect of flavonoids tested may be due to both the inhibition of thromboxane formation and thromboxane receptor antagonism.
Flavonoids: Antiplatelet Effect as Inhibitors of COX-1
Molecules, 2022
Flavonoids are compounds with a benzopyranic structure that exhibits multiple pharmacological activities. They are known for their venotonic activity, but their mechanism of action remains unclear. It is thought that, as this mechanism is mediated by prostaglandins, these compounds may interfere with the arachidonic acid (AA) cascade. These assays are designed to measure the antiplatelet aggregation capacity of quercetin, rutin, diosmetin, diosmin, and hidrosmin, as well as to evaluate a potential structure−activity ratio. In this paper, several studies on platelet aggregation at different concentrations (from 0.33 mM to 1.5 mM) of different flavone compounds are conducted, measuring platelet aggregation by impedance aggregometry, and the cyclooxygenase (COX) activity by metabolites generated, including the activity of the pure recombinant enzyme in the presence of these polyphenols. The results obtained showed that quercetin and diosmetin aglycones have a greater antiplatelet effec...
Influence of flavonoids’ lipophilicity on platelet aggregation
Acta Pharmaceutica
Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of...
Inhibitory effects of sulphated flavonoids isolated from Flaveria bidentis on platelet aggregation
Thrombosis Research, 2005
Flaveria bidentis is a plant species that has as major constituents sulphated flavonoids in the highest degree of sulphatation. Among them, quercetin 3,7,3V,4V-tetrasulphate (QTS) and quercetin 3-acetyl-7,3V,4V-trisulphate (ATS) are the most important constituents. Both showed anticoagulant properties. The objective of the present study was to evaluate the effects of these flavonoids on human platelet aggregation in comparison with the well-known inhibitor quercetin (Qc) by using several agonists. Platelet-rich plasma (PRP) or washed human platelets (WP) were incubated with different concentrations of the flavonoids to be tested (1 to 1000 AM, final concentration), and the platelet aggregation was induced by using adenosine 5V-diphosphate (ADP), epinephrine (EP), collagen, arachidonic acid (AA) and ristocetin as agonists. QTS (500 AM) and Qc ) markedly inhibited platelet aggregation with all the aggregant agents, except ristocetin, whereas ATS (1000 AM) showed only slight antiplatelet effects. In addition, QTS and Qc antagonized the aggregation 0049-3848/$ -see front matter D KEYWORDS Flaveria bidentis Sulphated flavonoids Antiplatelet activity Platelet aggregation Thrombosis Research (2005) 115, 495 -502
Impact of specific functional groups in flavonoids on the modulation of platelet activation
Scientific reports, 2018
Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4 carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related...
Food Chemistry, 2015
Chemical compounds studied in this article: Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7trihydroxychromen-4-one (PubChem CID: 5280343) Apigenin, 5,7-dihydroxy-2-(4hydroxyphenyl)chromen-4-one (PubChem CID: 5280443) 2-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, 1-4 (Chart 1) 2,3-Diphenyl-4H-pyrido[1,2-a]pyrimidin-4one derivatives, 5-7 (Chart 1)
Synthetic Flavonoids as Novel Modulators of Platelet Function and Thrombosis
International Journal of Molecular Sciences
Cardiovascular diseases represent a major cause of mortality and morbidity in the world, and specifically, thrombotic conditions such as heart attacks and strokes are caused by unwarranted activation of platelets and subsequent formation of blood clots (thrombi) within the blood vessels during pathological circumstances. Therefore, platelets act as a primary therapeutic target to treat and prevent thrombotic conditions. Current treatments are limited due to intolerance, and they are associated with severe side effects such as bleeding complications. Hence, the development of novel therapeutic strategies for thrombotic diseases is an urgent priority. Flavonoids are naturally occurring plant-derived molecules that exert numerous beneficial effects in humans through modulating the functions of distinct cell types. However, naturally occurring flavonoids suffer from several issues such as poor solubility, lipophilicity, and bioavailability, which hinder their efficacy and potency. Despi...
Traditionally Used Plants with the Inhibitory Effect of Platelet Aggregation
2018
During hemostasis, after vascular injury and wound healing process, platelets play a very significant role, where the platelets hypersensitivity is also related to the progression or development of various cardiovascular diseases. In this regard, there is a need to find such compounds, which provide more potent and safer activity against platelets with minimum side effects. This review article provided an overview of various medicinal plants having antiplatelet properties or pointed out the constituents associated with the activity, the part used for the isolation of plant constituents, and different pathways which mediate the antiplatelet activity. In this review different classes such as Liliaceae, Zingiberaceae, Rutaceae, Arecaceae and Asteraceae were suggested for their antiplatelet properties to which various medicinal plants belong possessing such properties. Specific bioactive components in different medicinal plants which relate to the antiplatelet properties are flavonoids,...
On the mechanism of antithrombotic action of flavonoids
Biochemical Pharmacology, 1987
Flavonols (quercetin and rutin) and flavanes (cyanidol and meciadonol) were studied for their effect on non-enzymatic lipid peroxidation, hpoxygenase and cycle-oxygenase activities, binding to albumin and platelet membranes. These biochemical properties of four flavonoids were compared with respect to their antithrombotic action in uivo and their efficacy at influencing the plateletendothelium interaction in vitro. AU four tlavonoids inhibited the ascorbate-stimulated formation of malondialdehyde by boiled rat liver microsomes (quercetin> rutin==cyanidol = meciadonol) and inhibited platelet lipoxygenase activity (quercetin > cyanidol > meciadonol > rutin) whereas only flavonols, but not flavanes, stimulated cyclo-oxygenase and were bound to platelet membranes. The same two flavonols dispersed platelet thrombi which were adhering to the rabbit aortic endotherm in vitro (ncsO for quer&in was*gOnM and for rutin SOOnM) and prevented platelets from aggregation over blood-su~~d collagen strip in vivo (ED~,, for quercetin was 5 mnol/kg and for rutin 33 nmol/kg Lv.). Cvanidol and me~adonol were not effective as ~ti-somatic agents. It is concluded that activated platelets adhering to vascular endothelium generate lipid peroxides and oxygen-free radicals which inhibit endothelial biosynthesis of prostacyclm and destroy endothelium-derived relaxing factor (EDRP). Plavonols are anti-thrombotic because they are selectively bound to mural platelet thrombi and owing to their free radical scavenging properties resuscitate biosynthesis and action of endothelial prostacyclin and EDRP. Thus, flavonois release the thrombolytic and vasoprotective endothelial mediators only in these vascular segments which are covered by a carpet of aggregating platelets.