Quercetin and its methylated metabolites possess anti-thrombotic properties that interact with aspirin to enhance its anti-platelet effects

Stainer, A., Sasikumar, P., Bye, A. ORCID: https://orcid.org/0000-0002-2061-2253, Unsworth, A., Holbrook, L., Tindall, M., Lovegrove, J. ORCID: https://orcid.org/0000-0001-7633-9455 and Gibbins, J. ORCID: https://orcid.org/0000-0002-0372-5352 (2019) Quercetin and its methylated metabolites possess anti-thrombotic properties that interact with aspirin to enhance its anti-platelet effects. TH Open, 3 (3). e244-e258. ISSN 2512-9465 doi: 10.1055/s-0039-1694028

Abstract/Summary

Quercetin, a dietary flavonoid, has been reported to possess anti-platelet activity. However, its extensive metabolism following ingestion has resulted in difficulty elucidating precise mechanisms of action. In this study, we aimed to characterise the anti-platelet 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 alphaIIbbeta3 function, calcium mobilisation, and Syk/LAT phosphorylation downstream of GPVI 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 anti-platelet effects of aspirin more-than-additively in a plate-based aggregometry assay, reducing aspirin IC50 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 anti-platelet activity of two quercetin metabolites, isorhamnetin and tamarixetin, and suggest a potential anti-thrombotic role for these flavonoids. In combination with their interactions with aspirin, this may represent a novel avenue of investigation for the development of new anti-thrombotic strategies and management of current therapies.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/84786
Identification Number/DOI	10.1055/s-0039-1694028
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords	Platelets, Quercetin, Aspirin, Flavonoids, Thrombosis
Publisher	Thieme
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