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 (IC(50)=11--69 microM). The oxygen functions (-OH, -OCH(3)) 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-kappa B activation following expression of inducible NO synthase.
Kageura
T
T
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Matsuda
H
H
Morikawa
T
T
Toguchida
I
I
Harima
S
S
Oda
M
M
Yoshikawa
M
M
D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D010946:Plants, Medicinal; D012250:Rheum / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*
D008070:Lipopolysaccharides; D013267:Stilbenes; D009569:Nitric Oxide