Resveratrol inhibits Ca²⁺ signals and aggregation of platelets

Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca²⁺-related mechanism for the inhibitory action of resveratrol on platelet aggregation.

Ca²⁺ entry and subsequent aggregation of human platelets induced by different stimulants including thrombin, thapsigargin, and 1-oleoyl-2-acetylglycerol (OAG) were measured by the fluorescence method and light transmittance method, respectively. Each stimulant was added to a nominally Ca²⁺-free medium containing platelets, and then CaCl₂ was added to the medium to induce Ca²⁺ influx into platelets.

Thapsigargin-induced Ca²⁺ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 6.25 μM or higher concentrations, while OAG-induced Ca²⁺ entry and subsequent platelet aggregation were not affected by resveratrol at concentrations up to 50 μM. In the nominally Ca²⁺-free medium, thrombin induced a small transient increase in intracellular Ca²⁺ concentrations, which was attenuated in the presence of resveratrol at 12.5 μM or higher concentrations. Thrombin-induced Ca²⁺ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 12.5 μM or higher concentrations.

The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca²⁺ release from its stores and inhibiting store-operated Ca²⁺ influx into platelets.