title: Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway.
abstract: BACKGROUND
  Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD.
  
  
  METHODS
  A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy.
  
  
  RESULTS
  Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression.
  
  
  CONCLUSIONS
  IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.
authors.affiliation: Key Laboratory of Liver and Kidney Diseases Ministry of Education, Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jin-Xing
authors.initials: JX
authors.lastname: Du
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Sun
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Du
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Mu
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Chen
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Long
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Bian
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.forename: Lie-Ming
authors.initials: LM
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D027883:Astragalus Plant; D027885:Astragalus propinquus; D001660:Biliary Tract Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003135:Common Bile Duct / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy; D008026:Ligation; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C027492:Huang Qi; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat