title: Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice.
abstract: This study was performed to examine the hepatoprotective effect of isorhamnetin-3-O-galactoside, a flavonoid glycoside isolated from Artemisia capillaris Thunberg (Compositae), against carbon tetrachloride (CCl4)-induced hepatic injury. Mice were treated intraperitoneally with vehicle or isorhamnetin-3-O-galactoside (50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20 μl/kg) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after CCl4 treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. CCl4 markedly increased serum tumor necrosis factor-α level, which was reduced by isorhamnetin-3-O-galactoside. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase- 2 (COX-2), and heme oxygenase-1 (HO-1) protein and their mRNA expression levels were significantly increased after CCl4 injection. The levels of HO-1 protein and mRNA expression levels were augmented by isorhamnetin-3-O-galactoside, while isorhamnetin- 3-O-galactoside attenuated the increases in iNOS and COX-2 protein and mRNA expression levels. CCl4 increased the level of phosphorylated c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38, and isorhamnetin-3-O-galactoside reduced these increases. The nuclear translocation of nuclear factor kappa B (NF-κB), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were signifi cantly increased after CCl4 administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-κB and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates CCl4-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Hong-Ik
authors.initials: HI
authors.lastname: Cho
authors.forename: Kang-Min
authors.initials: KM
authors.lastname: Kim
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
keywords: Carbon tetrachloride; Heme oxygenase-1; Hepatotoxicity; Inflammation; Isorhamnetin-3-O-galactoside; Oxidative stress