title: Antiplatelet Effects of Flavonoids Mediated by Inhibition of Arachidonic Acid Based Pathway.
abstract: Flavonoids, important components of human diet, have been claimed to possess a significant antiplatelet potential, in particular due to their effects on the arachidonic acid cascade. Due to variable and incomplete results, this study was aimed at delivering a detailed analysis of the effects of 29 structurally relevant, mainly natural flavonoids on three consecutive steps of the arachidonic acid cascade.Only the isoflavonoids genistein and daidzein were shown to possess a marked cyclooxygenase-1 inhibitory activity, which was higher than that of acetylsalicylic acid using the isolated ovine enzyme, and physiologically relevant, although lower than acetylsalicylic acid in human platelets. None of the tested flavonoids possesses an effect on thromboxane synthase in a clinically achievable concentration. Contrarily, many flavonoids, particularly those possessing an isolated 7-hydroxyl group and/or a 4'-hydroxyl group, acted as antagonists on thromboxane receptors. Interestingly, the substitution of the free 7-hydroxyl group by glucose might not abolish the activity.In conclusion, the consumption of few flavonoids in a diet, particularly of the isoflavonoids genistein and daidzein, may positively influence platelet aggregation.
authors.affiliation: Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Karlíčková
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Říha
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Filipský
authors.affiliation: Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Macáková
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Radomír
authors.initials: R
authors.lastname: Hrdina
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic.
authors.forename: Přemysl
authors.initials: P
authors.lastname: Mladěnka
mesh_terms: D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D013930:Thromboxane-A Synthase