The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide

Background: Epidemiologic studies have shown an inverse relation between moderate consumption of red wine and cardiovascular disease. Studies have shown that red wine and its component flavonoids inhibit in vivo platelet activation, but the underlying mechanism has not yet been identified. Objective: Because we showed previously that collagen-induced platelet aggregation is associated with a burst of hydrogen peroxide, which in turn contributes to stimulating the phospholipase C pathway, the aim of this study was to investigate whether flavonoids synergize in inhibiting platelet function and interfere with platelet function by virtue of their antioxidant effect. Design: We tested the effect of 2 flavonoids, quercetin and catechin, on collagen-induced platelet aggregation and hydrogen peroxide and on platelet adhesion to collagen. Results: Catechin (50-100 mu mol/L) and quercetin (10-20 mu mol/L) inhibited collagen-induced platelet aggregation and platelet adhesion to collagen. The combination of 25 mu mol catechin/L and 5 mu mol quercetin/L, neither of which had any effect on platelet function when used alone, significantly inhibited collagen-induced platelet aggregation and platelet adhesion to collagen. Such a combination strongly inhibited collagen-induced hydrogen peroxide production, calcium mobilization, and 1,3,4-inositol triphosphate formation. Conclusions: These data indicate that flavonoids inhibit platelet function by blunting hydrogen peroxide production and, in turn, phospholipase C activation and suggest that the synergism among flavonoids could contribute to an understanding of the relation between the moderate consumption of red wine and the decreased risk of cardiovascular disease.