Inhibition of prostaglandin E2 production by taiwanin C isolated from the root of Acanthopanax chiisanensis and the mechanism of action

Five lignans, I-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 (IC50 = 0.12 muM), followed by helioxanthin, cis-dibenzylbutyrolactone, and savinin. I-Sesamin had no effect. Taiwanin C showed no inhibitory effect on the TPA-induced release of radioactivity from [3 H] 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 (IC50 = 1.06 and 9.31 muM, 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. (C) 2002 Elsevier Science Inc. All rights reserved.