Inhibitors from rhubarb on lipopolysaccharide-induced nitric oxide production in macrophages: Structural requirements of stilbenes for the activity

By bioassay-guided separation, three stilbenes (rhapontigenin, piceatannol, and resveratrol), two stilbene glucoside gallates (rhaponticin 2''-O-gallate and rhaponticin 6"-O-gallate), and a naphthalene glucoside (torachrysone 8-O-beta -D-glucopyranoside) with inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages were isolated (IC50 = 11-69 muM). The oxygen functions (-OH, -OCH3) of stilbenes at the benzene ring were essential for the activity. The glucoside moiety reduced the activity, while the alpha,beta -double bond had no effect. Furthermore, the active stilbenes (rhapontigenin, piceatannol, and resveratrol) did not inhibit inducible NO synthase activity, but they inhibited nuclear factor-kappaB activation following expression of inducible NO synthase. (C) 2001 Elsevier Science Ltd. All rights reserved.