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THE RELATIONSHIP BETWEEN THE METABOLITES OF THE DIETARY FLAVONOID QUERCETIN AND HAEMOSTASIS, THROMBOSIS AND PLATELET FUNCTION
  1. AR Stainer1,
  2. JA Lovegrove2,
  3. JM Gibbins1
  1. 1Institute for Cardiovascular & Metabolic Research, University of Reading, Reading, UK
  2. 2Hugh Sinclair Unit of Human Nutrition, University of Reading, Reading, UK

Abstract

Flavonoids are plant secondary metabolites with beneficial effects on cardiovascular health. One notable flavonoid due to its anti-platelet properties is quercetin (3,3′,4′,5,7-pentahydroxyflavone). Upon consumption, quercetin is metabolized in the small intestine and liver, yielding methylated, sulphated and glucuronidated metabolites; their anti-platelet effects (function and signalling) and relevance at concentrations achieved in-vivo is not understood; a long term goal of my PhD is to investigate and model these effects.

Methods Platelet aggregation was performed by light-transmission aggregometry. Fibrinogen-binding and P-Selectin exposure were measured by flow cytometry.

Results Consistent with previous studies, quercetin inhibited collagen-stimulated (5 µg/ml) platelet aggregation in a dose-dependent manner; significant inhibition was observed as low as 3 µM (lower than previously reported). Above 6 µM, aggregation was inhibited >90%. In-vivo, numerous agonists are present at lower concentrations than typically used in in-vitro assays. Agonist concentrations that individually are subthreshold for aggregation, when added together, may synergise and stimulate substantial functional responses. The ability and potency of quercetin to inhibit fibrinogen-binding to platelets stimulated by this synergistic response between thrombin and CRP (Collagen-Related-Peptide) was therefore explored. Quercetin inhibited significantly fibrinogen-binding at concentrations as low as 500 nM. This was associated with substantial inhibition of alpha-granule secretion. Fibrinogen-binding and P-Selectin exposure stimulated by 0.1 µg/ml and 1 µg/ml CR P alone was also significantly inhibited by quercetin, at concentrations as low as 500 nM.

Conclusions Quercetin inhibits platelet function at concentrations lower than previously recognised and within potential physiological concentrations. Development of this work will allow elucidation and modelling of the effects of quercetin's main metabolites.

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