title: Betulinic acid prevention of d-galactosamine/lipopolysaccharide liver toxicity is triggered by activation of Bcl-2 and antioxidant mechanisms.
abstract: OBJECTIVE
  The hepatoprotective activity and molecular mechanism of betulinic acid (BA) was investigated on acute liver failure induced by d-galactosamine (D-GalN)/lipopolysaccharide (LPS) in vivo.
  
  
  METHODS
  Mice were administered with different doses of BA (20 mg/kg or 50 mg/kg, i.p.) 1 h before injection of D-GalN (700 mg/kg)/LPS (10 µg/kg) and sacrificed 6 h after treatment with D-GalN/LPS.
  
  
  RESULTS
  Pretreatment with BA significantly prevented the increases of serum aspartate aminotransferase and alanine aminotransferase, while it increased the content of glutathione and catalase, and reduced malondialdehyde. BA showed obvious anti-oxidant effects and prevented D-GalN/LPS-induced apoptosis, as indicated by DNA ladder. BA treatment resulted in regulation of the mitogen-activated protein kinase. We found that BA mediated production of c-jun NH(2) -terminal protein kinase and extracellular signal-regulated kinase induced by D-GalN/LPS, promoted the expression of B-cell CLL/lymphoma 2 (Bcl-2) and restored mitochondrial outer membrane permeabilization.
  
  
  CONCLUSIONS
  The results suggested that BA prevented D-GalN/LPS-induced acute liver failure by upregulation of Bcl-2 and antioxidation and mediation of cytokines causing apoptotic cell death and lessened liver damage.
authors.affiliation: Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province, China.
authors.forename: Zhan-Wei
authors.initials: ZW
authors.lastname: Zheng
authors.forename: Shun-Zong
authors.initials: SZ
authors.lastname: Song
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Lian
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Ji-Xing
authors.initials: JX
authors.lastname: Nan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000097:blood; D004195:Disease Models, Animal; D005688:Galactosamine; D005978:Glutathione / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects; D000094062:Betulinic Acid
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D008315:Malondialdehyde; D005688:Galactosamine; D002374:Catalase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D005978:Glutathione; D000094062:Betulinic Acid