(-)-Epigallocatechin gallate selectively inhibits adenosine diphosphate-stimulated human platelet activation: Suppression of heat shock protein 27 phosphorylation via p38 mitogen-activated protein kinase

(-)-Epigallocatechin gallate (EGCG) is a major component of green tea. It has been demonstrated that EGCG has an antithrombotic effect by inhibiting platelet aggregation. However, the detailed mechanisms underlying the effects of EGCG remain to be elucidated. The present study examined the effects of EGCG on human platelet activation by various stimulators and the exact underlying mechanisms. EGCG suppressed adenosine diphosphate (ADP)-stimulated platelet aggregation dose dependently between 30 and 70 μM. By contrast, EGCG failed to affect platelet aggregation stimulated by collagen, U46619 (a TP agonist) or ristocetin (an activator of GPIb/IX/V). EGCG attenuated the ADP-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase and heat shock protein 27 (HSP27). The ADP-stimulated release of platelet-derived growth factor (PDGF)-AB and the soluble CD40 (sCD40) ligand was inhibited by EGCG. These findings suggest that EGCG selectively inhibits ADP-stimulated human platelet activation and that EGCG reduces the release of PDGF-AB and the sCD40 ligand due to suppressing HSP27 phosphorylation via p38 MAP kinase.