title: (-)-Epigallocatechin gallate selectively inhibits adenosine diphosphate‑stimulated human platelet activation: suppression of heat shock protein 27 phosphorylation via p38 mitogen‑activated protein kinase.
abstract: (‑)‑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.
authors: Department of Anesthesiology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Yuko
authors: Y
authors: Iida
authors: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Tomoaki
authors: T
authors: Doi
authors: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Rie
authors: R
authors: Matsushima-Nishiwaki
authors: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Haruhiko
authors: H
authors: Tokuda
authors: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Shinji
authors: S
authors: Ogura
authors: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Osamu
authors: O
authors: Kozawa
authors: Department of Anesthesiology, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
authors: Hiroki
authors: H
authors: Iida
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012310:Ristocetin / Q000494:pharmacology; D013662:Tea / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010982:Platelet-Derived Growth Factor; D013662:Tea; C095477:platelet-derived growth factor AB; D012310:Ristocetin; D023201:CD40 Ligand; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002392:Catechin; C045651:epigallocatechin gallate; D048051:p38 Mitogen-Activated Protein Kinases