title: Hepatoprotective and antioxidant activities of extracts from Salvia-Nelumbinis naturalis against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet in mice.
abstract: BACKGROUND
  Nonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease that is characterized by both steatosis and severe injury in liver, still lacks efficient treatment. The traditional Chinese formula Salvia-Nelumbinis naturalis (SNN) is effectively applied to improve the symptoms of nonalcoholic simple fatty liver (NAFL) patients. Previous studies have confirmed that SNN could reduce the liver lipid deposition and serum transaminases of NAFL experimental models. This study aims to determine whether SNN is effective for murine NASH model and investigate the underlying pharmacological mechanisms.
  
  
  METHODS
  C57BL/6 J mice were fed with methionine- and choline-deficient (MCD) diet for six weeks to induce NASH. Simultaneously, SNN or saline was intragastrically administered daily to the mice in the SNN or model group, respectively. A standard diet was given to the control mice. Serum biochemical indices and tumor necrosis factor-α were measured. Liver histopathology was observed, and the contents of triglycerides and lipid peroxide malondialdehyde (MDA) in liver homogenates were evaluated. The hepatic expression and/or activation of genes associated with inflammation, apoptosis, and oxidative stress were determined by quantitative RT-PCR or Western blot analysis.
  
  
  RESULTS
  The prominent liver steatosis displayed in the NASH model was prevented by SNN. The liver injury of NASH mice was obviously manifested by the increased levels of serum transaminases and bilirubin, as well as the lobular inflammation, elevated pro-inflammatory cytokines, and upregulated apoptosis in liver tissues. SNN administration improved the aforementioned pathological changes. The increased hepatic levels of MDA and cytochrome P450 2E1 of the model confirmed the unregulated balance of oxidative stress. The hepatic expression of nuclear factor erythroid 2-related factor 2 and its target genes decreased, whereas c-Jun N-terminal kinase activation in the model mice increased. Treating the mice with SNN significantly improved oxidative stress-related harmful factors.
  
  
  CONCLUSIONS
  This study shows that SNN can protect the liver from severe steatosis and damage induced by MCD diet, which suggests the potential use of SNN on the treatment of NASH patient. The results also indicate that improving the hepatic antioxidant capability of the liver may contribute to the underlying hepatoprotective mechanism.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Song
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hanchen
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Shu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Dongfei
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. jiliver@vip.sina.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
mesh_terms: D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D002794:Choline / Q000032:analysis*; D017931:DNA Primers; D008099:Liver / Q000187:drug effects*; D008297:Male; D008715:Methionine / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D027544:Salvia / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D017931:DNA Primers; D010936:Plant Extracts; D008715:Methionine; D002794:Choline