Hepatoprotective principles from the flowers of Tilia argentea (linden): structure requirements of tiliroside and mechanisms of action.
The methanolic extract from the flowers of Tilia argentea (linden) was found to show a hepatoprotective effect against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. By bioassay-guided separation using in vitro D-GalN-induced damage to hepatocytes, five flavonol glycosides were isolated as the hepatoprotective constituents of the methanolic extract. Tiliroside, the principal flavonol glycoside, strongly inhibited serum GPT and GOT elevations at doses of 25-100 mg/kg (p.o.) in D-GalN/LPS-treated mice. By comparing the inhibitory effects of tiliroside with those of its components alone, the kaempferol 3-O-beta-D-glucopyranoside moiety was found to be essential for the activity, and its effect was suggested to depend on the inhibition of tumor necrosis factor-alpha (TNF-alpha) production, decreased sensitivity of hepatocytes to TNF-alpha, and on the protection of hepatocytes against D-GalN.
Matsuda
Hisashi
H
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Ninomiya
Kiyofumi
K
Shimoda
Hiroshi
H
Yoshikawa
Masayuki
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids; D005688:Galactosamine / Q000008:administration & dosage / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018514:Plant Structures; D029646:Tiliaceae / Q000737:chemistry*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C052083:tiliroside; D005688:Galactosamine; D002251:Carbon Tetrachloride; D019883:Alkyl and Aryl Transferases; C112459:geranylpyrophosphate olivetolate geranyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C106504:UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase