title: Novel bioactivity of ellagic Acid in inhibiting human platelet activation.
abstract: Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80  μ M) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80  μ M) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca(2+)] i mobilization, and the phosphorylation of phospholipase C (PLC) γ 2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt, as well as hydroxyl radical (OH(●)) formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.
authors.affiliation: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan ; School of Medicine, Fu Jen Catholic University, Taipei 242, Taiwan ; Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chang
authors.forename: Wei-Fan
authors.initials: WF
authors.lastname: Chen
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Lin
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Duen-Suey
authors.initials: DS
authors.lastname: Chou
authors.forename: Li-Jyun
authors.initials: LJ
authors.lastname: Lin
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Chang