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British Journal of Pharmacology








1 The phytoestrogenic compound trans-resveratrol (trans-3,5,4'-trihydroxystilbene) is found in appreciable quantities in grape skins and wine. It has been shown that both products rich in trans-resveratrol and pure trans-resveratrol inhibit platelet aggregation both in vivo and in vitro. However the mechanism of this action still remains unknown.

2 An essential component of the aggregation process in platelets is an increase in intracellular free Ca2+ ([Ca2+]i). Ca2+ must enter the cell from the external media through specific and tightly regulated Ca2+ channels in the plasma membrane. The objective of this study was to characterize what effect trans-resveratrol had on the Ca2+ channels in thrombin stimulated platelets.

3 In this study we showed that trans-resveratrol immediately inhibited Ca2+ influx in thrombin-stimulated platelets with an IC50 of 0.5 μM. trans-Resveratrol at 0.1, 1.0 and 10.0 μM produced 20 +/- 6, 37 +/- 6 and 57 +/- 4% inhibition respectively of the effect of thrombin (0.01 u ml-1) to increase [Ca2+]i.

4 trans-Resveratrol also inhibited spontaneous Ba2+ entry into Fura-2 loaded platelets, with 0.1, 1.0 and 10.0 μM trans-resveratrol producing 10 +/- 5, 30 +/- 5 and 50 +/- 7% inhibition respectively. This indicated that trans-resveratrol directly inhibited Ca2+ channel activity in the platelets in the absence of agonist stimulation.

5 trans-Resveratrol also inhibited thapsigargin-mediated Ca2+ influx into platelets. This suggests that the store-operated Ca2+ channels are one of the possible targets of trans-resveratrol. These channels rely on the emptying of the internal Ca2+ stores to initiate influx of Ca2+ into the cell.

6 The phytoestrogens genistein, daidzein, apigenin and genistein-glucoside (genistin) produced inhibitory effects against thrombin similar to those seen with trans-resveratrol.

7 We conclude that trans-resveratrol is an inhibitor of store-operated Ca2+ channels in human platelets. This accounts for the ability of trans-resveratrol to inhibit platelet aggregation induced by thrombin.


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Original Publication Citation

Dobrydneva, Y., Williams, R. L., & Blackmore, P. F. (1999). trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. British Journal of Pharmacology, 128(1), 149-157. doi:10.1038/sj.bjp.0702749