title: Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl(4)-intoxicated mice.
abstract: This study investigated the protective effects of isoquinoline alkaloid berberine on the CCl(4)-induced hepatotoxicity in mice. Berberine was administered as a single dose at 5 and 10mg/kg intraperitoneally (i.p.), 1h before CCl(4) (10%, v/v in olive oil, 2ml/kg) injection and mice were euthanized 24h later. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl(4)-intoxicated mice was markedly suppressed by berberine in a concentration-dependent manner. The decrease in hepatic activity of superoxide dismutase (Cu/Zn SOD) and an increase in lipid peroxidation were significantly prevented by berberine. Histopathological changes were reduced and the expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was markedly attenuated by berberine 10mg/mg. The results of this study indicate that berberine could be effective in protecting the liver from acute CCl(4)-induced injury. The hepatoprotective mechanisms of berberine may be related to the free radical scavenging and attenuation of oxidative/nitrosative stress, as well as to the inhibition of inflammatory response in the liver.
authors.affiliation: Department of Chemistry and Biochemistry, School of Medicine, University of Rijeka, B. Branchetta 20, Rijeka, Croatia. robertd@medri.hr
authors.forename: Robert
authors.initials: R
authors.lastname: Domitrović
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Jakovac
authors.forename: Gordana
authors.initials: G
authors.lastname: Blagojević
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase