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  • Title: Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity.
    Author: Jin YR, Han XH, Zhang YH, Lee JJ, Lim Y, Chung JH, Yun YP.
    Journal: Atherosclerosis; 2007 Sep; 194(1):144-52. PubMed ID: 17092506.
    Abstract:
    Diet can be one of the most important factors that influence risks for atherothrombotic diseases. Hesperetin included in grapefruits and oranges is one candidate that may benefit the cardiovascular system. Here, we investigated antiplatelet activity of hesperetin in vitro. In addition, possible antiplatelet mechanism was also investigated. Hesperetin concentration-dependently inhibited washed rabbit platelet aggregation induced by collagen and arachidonic acid, with IC50 of 20.5+/-3.5 and 69.2+/-5.1 microM, respectively, while has little effect on thrombin- or U46619-, a thromboxane (TX) A2 mimic, mediated platelet aggregation, suggesting that hesperetin may selectively inhibit collagen- and arachidonic acid-mediated signal transduction. In accordance with these findings, hesperetin revealed blocking of the collagen-mediated phospholipase (PL) C-gamma2 phosphorylation, and caused concentration-dependent decreases of cytosolic calcium mobilization, arachidonic acid liberation and serotonin secretion. In addition, hesperetin inhibited arachidonic acid-mediated platelet aggregation by interfering with cyclooxygenase-1 activity as established by the measurement of arachidonic acid-mediated TXA2 and prostaglandin D2 formations as well as cyclooxygenase-1 and TXA2 synthase activity assays. Taken together, the present results provide a cellular mechanism for the antiplatelet activity of hesperetin through inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity, which may contribute to the beneficial effects of grapefruits and oranges on cardiovascular system.
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