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 mo derate consumption of red wine and cardiovascular disease. Studies have sho wn that red wine and its component flavonoids inhibit in vivo platelet acti vation, but the underlying mechanism has not yet been identified. Objective: Because we showed previously that collagen-induced platelet aggr egation is associated with a burst of hydrogen peroxide, which in turn cont ributes to stimulating the phospholipase C pathway, the aim of this study w as to investigate whether flavonoids synergize in inhibiting platelet funct ion and interfere with platelet function by virtue of their antioxidant eff ect. Design: We tested the effect of 2 flavonoids, quercetin and catechin, on co llagen-induced platelet aggregation and hydrogen peroxide and on platelet a dhesion to collagen. Results: Catechin (50-100 mu mol/L) and quercetin (10-20 mu mol/L) inhibite d collagen-induced platelet aggregation and platelet adhesion to collagen. The combination of 25 mu mol catechin/L and 5 mu mol quercetin/L, neither o f which had any effect on platelet function when used alone, significantly inhibited collagen-induced platelet aggregation and platelet adhesion to co llagen. Such a combination strongly inhibited collagen-induced hydrogen per oxide production, calcium mobilization, and 1,3,4-inositol triphosphate for mation. Conclusions: These data indicate that flavonoids inhibit platelet function by blunting hydrogen peroxide production and, in turn, phospholipase C acti vation and suggest that the synergism among flavonoids could contribute to an understanding of the relation between the moderate consumption of red wi ne and the decreased risk of cardiovascular disease.