title: Protective effects of calycosin against CCl4-induced liver injury with activation of FXR and STAT3 in mice.
abstract: OBJECTIVE
  Investigating the hepatoprotective effect of calycosin against acute liver injury in association with FXR activation and STAT3 phosphorylation.
  
  
  METHODS
  The acute liver injury model was established by intraperitoneal injection of CCl4 in C57BL/6 mice. Serum alanine aminotransferase, aspartate aminotransferase, HE staining and TUNEL assay were used to identify the amelioration of the liver histopathological changes and hepatocytes apoptosis after calycosin treatment. ELISA kit and 5-bromo-2-deoxyuridine immunohistochemistry were used to measure the liver bile acid concentration and hepatocyte mitotic rate in vivo. The relation between calycosin and activation of FXR and STAT3 was comfirmed using the Luciferase assay, Molecular docking, Real-time PCR and Western Blot in vitro.
  
  
  RESULTS
  The liver histopathological changes, hepatocytes apoptosis, liver bile acid overload and hepatocyte mitosis showed significant changes after calycosin treatment. Calycosin promoted the expression of FXR target genes such as FoxM1B and SHP but the effect was reversed by FXR suppressor guggulsterone. Molecular docking results indicated that calycosin could be embedded into the binding pocket of FXR, thereby increasing the expressions of STAT3 tyrosine phosphorylation and its target genes, Bcl-xl and SOCS3.
  
  
  CONCLUSIONS
  Calycosin plays a critical role in hepatoprotection against liver injury in association with FXR activation and STAT3 phosphorylation.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian, Liaoning, 116044, People's Republic of China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Huo
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D007529:Isoflavones / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D002251:Carbon Tetrachloride; D004365:Drugs, Chinese Herbal; D007529:Isoflavones; D020011:Protective Agents; D018160:Receptors, Cytoplasmic and Nuclear; D050796:STAT3 Transcription Factor; D000099150:Receptor, Farnesoid X-Activated; C494087:Stat3 protein, mouse; C121707:7,3'-dihydroxy-4'-methoxyisoflavone