Inhibitors from Rhubarb on Lipopolysaccharide-Induced Nitric Oxide Production in Macrophages: Structural Requirements of Stilbenes for the Activity Original Research Article

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-β-d-glucopyranoside) with inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages were isolated (IC50=11–69 μM). The oxygen functions (–OH, –OCH3) of stilbenes at the benzene ring were essential for the activity. The glucoside moiety reduced the activity, while the α,β-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-κB activation following expression of inducible NO synthase.