Resveratrol attenuates thromboxane A2 receptor agonist-induced platelet activation by reducing phospholipase C activity

Resveratrol (3,5,4′-trihydroxystilbene) is a naturally occurring compound shown to decrease the incidence of thromboembolic disease. Although considerable data are available as to the inhibitory effect of resveratrol on the platelet aggregation and thrombopoiesis in human, its underlying mechanism, at the cellular level, has not been rigorously studied. In this experiment, we studied the effect of resveratrol and 1-[6-[[17-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione, a phospholipase C inhibitor (U-73122) on the thromboxane A2 receptor agonist (9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α, U46619)-induced platelet aggregation, platelet P-selectin expression, and the activity of phospho-phospholipase C β3 (P-PLC β3) and total-phospholipase C β3 (T-PLC β3), which play key roles in the signal transduction system of platelet in human. It was found that resveratrol blocked platelet aggregation and platelet P-selectin expression induced by U46619 in a concentration-dependent manner. U-73122 and resveratrol had additive effect in inhibiting platelet aggregation and platelet P-selectin expression. Resveratrol (final concentration was 50 µM) could reduce the ratio of P-PLC β3 to T-PLC β3. Taken together, these results show that resveratrol suppresses U46619-induced platelet aggregation and P-selectin expression partly through the decrease of the activity of phospholipase C β of platelets.