Effects of sesquiterpenes and triterpenes from the rhizome of Alisma orientale on nitric oxide production in lipopolysaccharide-activated macrophages: absolute stereostructures of alismaketones-B 23-acetate and -C 23-acetate.
The methanolic extract from a Chinese herbal medicine, the rhizome of Alisma orientale, was found to exhibit inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)activated macrophages. Novel triterpenes, alismaketones-B 23-acetate and -C 23-acetate, were isolated from the active extract together with eight sesquiterpenes and eighteen protostane-type triterpenes. The absolute stereostructures of new triterpenes were characterized on the basis of chemical and physicochemical evidence, which included the chemical correlations with known triterpenes. The guaiane-type sesquiterpenes (alismol, orientalols A and C) and protostane- and seco-protostane-types triterpenes (alisols C monoacetate, E-23-acetate, F, H, I, L-23-acetate, and M-23-acetate, alismaketones-B 23-acetate and -C 23-acetate, alismalactone 23-acetate, and 3-methylalismalactone 23-acetate) inhibited LPS-induced NO production (IC50 = 8.4-68 microM). Other triterpenes (alisols A, A monoacetate, B, B monoacetate, E, G, K-23-acetate, and N-23-acetate and 11-deoxyalisol B) also showed the potent inhibitory activity, but they showed cytotoxic effects more than 30 microM (MTT assay). In addition, alismol and alisol F were found to suppress iNOS induction.
Matsuda
H
H
Kyoto Pharmaceutical University, Misasagi, Japan.
Kageura
T
T
Toguchida
I
I
Murakami
T
T
Kishi
A
A
Yoshikawa
M
M
D000818:Animals; D002783:Cholestenones / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D012717:Sesquiterpenes / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*
D002783:Cholestenones; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; D014315:Triterpenes; C400927:alismaketone-B 23-acetate; C400928:alismaketone-C 23-acetate; C516685:alisol F; C000050:alisol A; D009569:Nitric Oxide; C053720:alismol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse