title: Hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase.
abstract: OBJECTIVE
  We investigated the protective effect of berberine (BBR) on chronic liver fibrosis in mice and the potential mechanism underlying the activation of AMP-activated protein kinase (AMPK) pathway.
  
  
  METHODS
  CCl4-induced chronic liver fibrosis model in mice was established and activated rat hepatic stellate cell was treated with BBR. Cell viability was evaluated by SRB assay and protein expressions were detected by Western blot.
  
  
  RESULTS
  Our results showed that BBR ameliorated the liver fibrosis in mice with CCl4-induced liver injury and inhibited the proliferation of hepatic stellate cell in dose- and time-dependent manner. BBR decreased the enzyme release of ALT, AST, and ALP in serum, elevated SOD and reduced MDA content of liver tissue in CCl4-induced liver fibrosis model. BBR delayed the formation of regenerative nodules and reduced necrotic areas compared to CCl4 group. Moreover, BBR treatment activated AMPK, decreased the protein expression of Nox4, TGF-β1 and the phosphorylated Akt. The expression of smooth muscle actin (α-SMA), the marker of activated hepatic stellate cell, was also reduced by BBR treatment.
  
  
  CONCLUSIONS
  Our studies firstly demonstrated that BBR exerted hepatoprotective effects possibly via activation of AMPK, blocking Nox4 and Akt expression. Our findings may benefit the development of new strategies in the prevention of chronic liver disease.
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Mujie
authors.initials: M
authors.lastname: Kan
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Xuanang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Yunjing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, China-Japan Union Hospital of Jilin University, Jilin University, China. Electronic address: zxw515@sohu.com.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, China. Electronic address: zhouweichen@yahoo.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats
chemical_list: D020536:Enzyme Activators; D001599:Berberine; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Akt; Berberine; Liver fibrosis; ROS