Inhibition of prostaglandin E(2) production by taiwanin C isolated from the root of Acanthopanax chiisanensis and the mechanism of action.
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.
Ban
Hyun Seung
HS
Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, 980-8578, Miyagi, Japan.
Lee
Sanghyun
S
Kim
Yong Pil
YP
Yamaki
Kouya
K
Shin
Kuk Hyun
KH
Ohuchi
Kazuo
K
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
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