The Metabolites of the Dietary Flavonoid Quercetin Possess Potent Antithrombotic Activity, and Interact with Aspirin to Enhance Antiplatelet Effects

TH Open : Companion Journal to Thrombosis and Haemostasis
Alexander R StainerJonathan M Gibbins

Abstract

Quercetin, a dietary flavonoid, has been reported to possess antiplatelet activity. However, its extensive metabolism following ingestion has resulted in difficulty elucidating precise mechanisms of action. In this study, we aimed to characterize the antiplatelet mechanisms of two methylated metabolites of quercetin-isorhamnetin and tamarixetin-and explore potential interactions with aspirin. Isorhamnetin and tamarixetin inhibited human platelet aggregation, and suppressed activatory processes including granule secretion, integrin αIIbβ3 function, calcium mobilization, and spleen tyrosine kinase (Syk)/linker for activation of T cells (LAT) phosphorylation downstream of glycoprotein VI with similar potency to quercetin. All three flavonoids attenuated thrombus formation in an in vitro microfluidic model, and isoquercetin, a 3-O-glucoside of quercetin, inhibited thrombosis in a murine laser injury model. Isorhamnetin, tamarixetin, and quercetin enhanced the antiplatelet effects of aspirin more-than-additively in a plate-based aggregometry assay, reducing aspirin IC 50 values by an order of magnitude, with this synergy maintained in a whole blood test of platelet function. Our data provide mechanistic evidence for the antiplatelet...Continue Reading

Citations

Dec 28, 2019·International Journal of Molecular Sciences·Borkwei Ed NignpenseAbishek B Santhakumar
Jun 13, 2020·Platelets·Fawaz O Alenazy, Mark R Thomas
Jun 23, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Qian DengJingui Xue
Jan 23, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jerzy ŻuchowskiBeata Olas
Apr 17, 2021·Frontiers in Cardiovascular Medicine·Olina DagherMichel Carrier
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rosa Edith Grijalva-GuizaLuis Ricardo Hernández
Jul 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Cristina ZaragozáMelchor Álvarez-Mon
Aug 8, 2021·Foods·Borkwei Ed NignpenseAbishek Bommannan Santhakumar
Jul 30, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tapan BehlDanut-Eugeniu Mosteanu

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