Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activities |
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Authors: | Ji-Yeon Yu Jung-Jin Lee Jae-Kyung Jung Yong-Ki Min Jin Yeul Ma Tack-Joong Kim Mi-Yea Lee Yeo-Pyo Yun |
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Institution: | 1. Laboatory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon, 305-600, Korea 2. Korean Medicine (KM)-Based Herbal Drug Research Group, Korea Institute of Oriental Medicine, Daejeon, 305-811, Korea 3. College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, 361-763, Korea 4. Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju, 220-710, Korea 5. Department of Nursing, Kyungbok University, Pocheon, 487-717, Korea
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Abstract: | Obovatol has been reported biological activities such as muscle relaxative, anti-gastric ulcer, anti-allergic and anti-bacterial activities. The present study was undertaken to investigate the effect of diacetylated obovatol, an obovatol derivative, on rabbit platelet aggregation, and their possible molecular mechanisms. Effects of diacetylated obovatol on platelet activation including aggregation and serotonin secretion were examined. In addition, we investigated the effect of diacetylated obovatol on archidonic acid and metabolites liberation and intracellular calcium mobilization. Diacetylated obovatol concentration-dependently inhibited the washed rabbit platelet aggregation induced by collagen and arachidonic acid, suggesting that diacetylated obovatol may selectively inhibits collagen- and arachidonic acid-mediated signal transduction. In accordance with these results, diacetylated obovatol showed a concentrationdependent decrease in cytosolic Ca2+ mobilization and serotonin secretion. However, diacetylated obovatol did not inhibit arachidonic acid liberation; on the other hand, diacetylated obovatol inhibited the formation of arachidonic acid metabolites such as thromboxane A2, prostaglandin D2 and 12-HETE through interfering with cyclooxygenase (COX)-1 and lipoxygenase (LOX) activities. The results demonstrated that diacetylated obovatol has antiplatelet activities through inhibition of COX-1 and LOX activities. |
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