Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl(4)-induced toxicity: action mechanism and structure-activity relationship.
Phenylpropanoids isolated from the roots of Scrophularia buergeriana MIQ. (Scrophulariaceae) protected primary cultures of rat hepatocytes from toxicity induced by carbon tetrachloride (CCl(4) ). In this report, we show that two of these phenylpropanoids, 4-O-E- p-methoxycinnamoyl-alpha-L-rhamnopyranoside ester ( 1) and p-methoxycinnamic acid ( 3) have significant hepatoprotective activity; another phenylpropanoid used for comparison, isoferulic acid ( 11), was equally active. To determine the mechanism(s) by which these three phenylpropanoids exerted their hepatoprotective activity, we measured activities of enzymes involved in the glutathione (GSH) redox system and assayed the level of hepatic mitochondrial GSH. The GSH levels in primary cultures of rat hepatocytes were significantly reduced with CCl(4) insult, but were significantly preserved by the treatment with these three phenylpropanoids. The activities of glutathione disulfide reductase and glutathione-S-transferase which normally decrease in CCl(4) -injured rat hepatocytes were significantly preserved by the treatment with these three phenylpropanoids. In addition, in CCl(4) -injured rat hepatocytes, the increased formation of malondialdehyde, a byproduct of lipid peroxidation, was reduced by the treatment with these phenylpropanoids. We determined the essential structural moiety within these three phenylpropanoids needed to exert hepatoprotective activity. The alpha,beta-unsaturated ester moiety seemed to be essential for exerting hepatoprotective activity.
Lee
Eun Ju
EJ
College of Pharmacy, Seoul National University, Seoul, Korea.
Kim
So Ra
SR
Kim
Jinwoong
J
Kim
Young Choong
YC
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D002934:Cinnamates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase; D005982:Glutathione Transferase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010666:Phenylpropionates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D012210:Rhamnose / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D028083:Scrophulariaceae; D013880:Thioredoxin-Disulfide Reductase
C462024:4-O-(4-methoxycinnamoyl) rhamnopyranoside; D002934:Cinnamates; D010666:Phenylpropionates; D010936:Plant Extracts; D008315:Malondialdehyde; C063318:4-methoxycinnamic acid; D002251:Carbon Tetrachloride; D009247:NADH, NADPH Oxidoreductases; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; C424443:Txnrd3 protein, mouse; D005982:Glutathione Transferase; D005978:Glutathione; D012210:Rhamnose; C008180:isoferulic acid