Isorhamnetin-3-O-galactoside Protects against CCl4-Induced Hepatic Injury in Mice

  • Kim, Dong-Wook (School of Pharmacy, Sungkyunkwan University) ;
  • Cho, Hong-Ik (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Kang-Min (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, So-Jin (School of Pharmacy, Sungkyunkwan University) ;
  • Choi, Jae-Sue (Faculty of Food Science and Biotechnology, Pukyoung National University) ;
  • Kim, Yeong-Shik (College of Pharmacy, Seoul National University) ;
  • Lee, Sun-Mee (School of Pharmacy, Sungkyunkwan University)
  • Received : 2012.07.04
  • Accepted : 2012.07.16
  • Published : 2012.07.31


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 ($CCl_4$)-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 $CCl_4$ (20 ${\mu}l/kg$) injection. Serum aminotransferase activities and hepatic level of malondialdehyde were significantly higher after $CCl_4$ treatment, and these increases were attenuated by isorhamnetin-3-O-galactoside. $CCl_4$ markedly increased serum tumor necrosis factor-${\alpha}$ 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 $CCl_4$ 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. $CCl_4$ 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-${\kappa}B$), activating protein-1, and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly increased after $CCl_4$ administration. Isorhamnetin-3-O-galactoside attenuated the increases of NF-${\kappa}B$ and c-Jun nuclear translocation, while it augmented the nuclear level of Nrf2. These results suggest that isorhamnetin-3-O-galactoside ameliorates $CCl_4$-induced hepatic damage by enhancing the anti-oxidative defense system and reducing the inflammatory signaling pathways.


Carbon tetrachloride;Heme oxygenase-1;Hepatotoxicity;Inflammation;Isorhamnetin-3-O-galactoside;Oxidative stress


Grant : Studies on the Identifi cation of Efficacy of Biologically Active Components from Oriental Herbal Medicines

Supported by : Korea Food and Drug Administration


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