title: Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activities.
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 concentration-dependent decrease in cytosolic Ca(2+) 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 A(2), prostaglandin D(2) 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.
authors.affiliation: Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Yu
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.forename: Tack-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Mi-Yea
authors.initials: MY
authors.lastname: Lee
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits
chemical_list: D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D010975:Platelet Aggregation Inhibitors; C036795:obovatol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases