title: Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice.
abstract: Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl(4))-induced liver injury. The mice were treated intraperitoneally with CCl(4) (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl(4). The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl(4) treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl(4) increased the level of circulating tumor necrosis factor-alpha markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl(4) treatment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl(4) increased the level of tumor necrosis factor-alpha, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl(4)-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Gyeonggi-do, Korea.
authors.forename: Chan-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Park
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019695:Glycyrrhizic Acid; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione