title: Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.
abstract: In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl₄-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl₄ injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl₄ control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl₄-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.
authors.affiliation: Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju 561-712, Korea.
authors.forename: Prabodh
authors.initials: P
authors.lastname: Risal
authors.forename: Pyoung Han
authors.initials: PH
authors.lastname: Hwang
authors.forename: Bong Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
authors.forename: Baik Hwan
authors.initials: BH
authors.lastname: Cho
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Yeon Jun
authors.initials: YJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D007783:Lactones; D011753:Pyrones; D014409:Tumor Necrosis Factor-alpha; C068766:davallialactone; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; C007946:hispidin