title: Fuzheng Huayu recipe prevents nutritional fibrosing steatohepatitis in mice.
abstract: BACKGROUND
  Fuzheng Huayu recipe (FZHY), a compound of Chinese herbal medicine, was reported to improve liver function and fibrosis in patients with hepatitis B virus infection. However, its effect on nutritional fibrosing steatohepatitis is unclear. We aimed to elucidate the role and molecular mechanism of FZHY on this disorder in mice.
  
  
  METHODS
  C57BL/6 J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrosing steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice, respectively. The effect of FZHY was assessed by comparing the severity of hepatic injury, levels of hepatic lipid peroxides, activation of hepatic stellate cells (HSCs) and the expression of oxidative stress, inflammatory and fibrogenic related genes.
  
  
  RESULTS
  Mice fed with MCD diet for 8 weeks showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. Administration of FZHY or hemin significantly lowered serum levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. An additive effect was observed in mice fed MCD supplemented with FZHY or/and hemin. These effects were associated with down-regulation of pro-oxidative stress gene cytochrome P450 2E1, up-regulation of anti-oxidative gene HO-1; suppression of pro-inflammation genes tumor necrosis factor alpha and interleukin-6; and inhibition of pro-fibrotic genes including α-smooth muscle actin, transforming growth factor beta 1, collagen type I (Col-1) and Col-3.
  
  
  CONCLUSIONS
  Our study demonstrated the protective role of FZHY in ameliorating nutritional fibrosing steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Jia
authors.forename: Rong-Qi
authors.initials: RQ
authors.lastname: Wang
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Mi
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Kong
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Ren
authors.forename: Wen-Cong
authors.initials: WC
authors.lastname: Li
authors.forename: Su-Xian
authors.initials: SX
authors.lastname: Zhao
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zhang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wu
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Nan
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006427:Hemin / Q000627:therapeutic use; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
chemical_list: D000199:Actins; D000975:Antioxidants; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D012333:RNA, Messenger; C544013:alpha-smooth muscle actin, mouse; C532829:fuzheng huayu; D006427:Hemin; D019392:Cytochrome P-450 CYP2E1; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse