title: Modulation of IKKβ/NF-κB and TGF-β1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice.
abstract: OBJECTIVE
  Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body's resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor κB kinase-β (IKK-β)/nuclear factor-κB (NF-κB) and transforming growth factor beta 1 (TGF-β1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice.
  
  
  METHODS
  C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice. The effects of FZHY alone and in combination with hemin were assessed by comparing the severity of hepatic injury, activation of hepatic stellate cells (HSCs), and the expression of oxidative stress, inflammation and fibrogenesis related genes.
  
  
  RESULTS
  Administration of FZHY, hemin and FZHY plus hemin significantly ameliorated liver injury. Additionally, our analysis indicated that administration of these agents significantly attenuated oxidative stress, downregulated the expression of pro-inflammatory and pro-fibrotic genes, including IKK-β, NF-κB, monocyte chemoattractant protein-1 (MCP-1), α-smooth muscle actin (α-SMA), TGF-β1, Smad3 and Smad4, and upregulated the expression of the antifibrogenic gene Smad7 (P< 0.001).
  
  
  CONCLUSIONS
  FZHY-containing therapies prevented nutritional steatohepatitis and fibrosis through modulating the expression of factors associated with the IKKβ/NF-κB and TGF-β1/Smad signaling pathways and oxidative stress related genes.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Rong-Qi
authors.initials: RQ
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Mi
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Su-Xian
authors.initials: SX
authors.lastname: Zhao
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.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Nan
keywords: FuzhengHuayu; Heme oxygenase-1; Hepatic fibrosis; IKK-β/NF-κB signaling pathway; Non-alcoholic steatohepatitis; TGF-β1/Smad signaling pathway