title: Inhibition of prostaglandin E(2) production by taiwanin C isolated from the root of Acanthopanax chiisanensis and the mechanism of action.
abstract: Five lignans, l-sesamin, savinin, helioxanthin, taiwanin C, and cis-dibenzylbutyrolactone, were isolated from the root of Acanthopanax chiisanensis (Araliaceae), a Korean medicinal plant, and their inhibitory effects on the production of prostaglandin (PG) E(2) stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) in rat peritoneal macrophages were examined. Among the five lignans, taiwanin C was the most potent (IC(50)=0.12 microM), followed by helioxanthin, cis-dibenzylbutyrolactone, and savinin. l-Sesamin had no effect. Taiwanin C showed no inhibitory effect on the TPA-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages, nor did it inhibit the expression of cyclooxygenase (COX)-2 protein induced by TPA. However, the activities of isolated COX-1 and COX-2 were inhibited by taiwanin C (IC(50)=1.06 and 9.31 microM, respectively), reflecting the inhibition of both COX-1- and COX-2-dependent PGE(2) production in the cell culture system. These findings suggest that the mechanism of action of taiwanin C in the inhibition of PGE(2) production is the direct inhibition of COX enzymatic activity.
authors.affiliation: Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, 980-8578, Miyagi, Japan.
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Ban
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Kim
authors.forename: Kouya
authors.initials: K
authors.lastname: Yamaki
authors.forename: Kuk Hyun
authors.initials: KH
authors.lastname: Shin
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohuchi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D027481:Araliaceae / Q000737:chemistry*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D018517:Plant Roots / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014316:Tritium
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007783:Lactones; D017705:Lignans; D008565:Membrane Proteins; C467766:taiwanin C; D014316:Tritium; D016718:Arachidonic Acid; D019284:Thapsigargin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D019311:Staurosporine; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate