CC BY 4.0 · TH Open 2019; 03(03): e244-e258
DOI: 10.1055/s-0039-1694028
Original Article
Georg Thieme Verlag KG Stuttgart · New York

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

Alexander R. Stainer
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
Parvathy Sasikumar
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
2   Centre for Haematology, Imperial College London, London, United Kingdom
Alexander P. Bye
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
Amanda J. Unsworth
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
3   School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom
Lisa M. Holbrook
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
4   School of Cardiovascular Medicine and Sciences, King's College London, London, United Kingdom
Marcus Tindall
5   Department of Mathematics and Statistics, University of Reading, Reading, United Kingdom
Julie A. Lovegrove
6   Department of Food and Nutritional Sciences, Hugh Sinclair Unit of Human Nutrition, University of Reading, Reading, United Kingdom
Jonathan M. Gibbins
1   Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, United Kingdom
› Author Affiliations
Funding This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC, grant GS13-04), British Heart Foundation (PG/15/21/31355, PG/13/93/30593, RG/09/011/28094, and RG/15/2/31224), and Medical Research Council (MR/J002666/1).
Further Information

Publication History

20 December 2018

24 June 2019

Publication Date:
30 July 2019 (online)


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 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 antiplatelet activity of two quercetin metabolites, isorhamnetin and tamarixetin, and suggest a potential antithrombotic role for these flavonoids. In combination with their interactions with aspirin, this may represent a novel avenue of investigation for the development of new antithrombotic strategies and management of current therapies.

Supplementary Material

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