Resveratrol Decreases Early Signaling Events in Washed Platelets but Has Little Effect on Platelet Aggregation in Whole Blood

Abstract ABSTRACT Resveratrol, a polyphenolic compound found in red wines, is believed to be a contributor in decreasing the incidence of coronary heart disease. Although its primary target is unknown, it blocks aggregation of washed platelets by an ill-defined mechanism. We show that resveratrol, at 10–50 μM, blocked aggregation induced by collagen (5 μg/ml), thrombin (0.2 units/ml), and ADP (10 μM). This affect was not overcome by adding exogenous human fibrinogen to the assay, suggesting that an early (wave I) signaling step in the α IIb β 3 activation cascade was impaired. To explore this possibility we examined the effect of resveratrol on activation of MAP kinases. In the platelet, MAP kinases become activated as a consequence of agonist binding and not of aggregation, which itself induces signaling events. In fact, we find that collagen-induced activation of MAP kinases is superinduced in the presence of RGDS, an aggregation-blocking peptide. Resveratrol, at concentrations of 10 μM and greater, inhibited MAP kinase activation induced by collagen (in the absence and presence of RGDS peptide), thrombin, and ADP. These data indicate that resveratrol blocks receptor-mediated signaling events in washed platelets. In comparison, resveratrol has poor antiplatelet activity in whole blood. Under these conditions aggregation was not affected by 50–100 μM resveratrol. Concentrations of 200 μM resveratrol were needed to cause a 30–60% decrease in platelet aggregation in whole blood. Together these studies suggest that resveratrol is a potent inhibitor of platelet signaling responses, but its antiplatelet activity is weakened or masked in circulation. Thus, although resveratrol may function as a protective agent of coronary heart disease, its affects are not solely attributed to its effects on platelets in circulation.