title: Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury.
abstract: OBJECTIVE
  To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing factors.
  
  
  METHODS
  Liver fibrosis was induced by administration of CCl4 for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, α-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and α-SMA mRNA, collagen type I and III mRNA were estimated by real-time PCR.
  
  
  RESULTS
  Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl4-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl4-treated group. The expression levels of cleaved caspase-3, Bax, α-SMA, CTGF, MMP2 and MMP9 proteins, and α-SMA mRNA, collagen type I and III mRNA were also significantly reduced by GA compared with the CCl4-treated group (P < 0.05).
  
  
  CONCLUSIONS
  GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation.
authors.affiliation: Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Guo
authors.affiliation: Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Ma
authors.affiliation: Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China.
authors.forename: Zheng-Quan
authors.initials: ZQ
authors.lastname: Feng
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D019610:Cytoprotection; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002251:Carbon Tetrachloride; D053148:Caspase 3; D024042:Collagen Type I; D024061:Collagen Type III; D055513:Connective Tissue Growth Factor; D019695:Glycyrrhizic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020011:Protective Agents; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat; C505410:Casp3 protein, rat; C522363:Mmp2 protein, rat; C572337:Mmp9 protein, rat
keywords: Glycyrrhizic acid; Hepatic stellate cell; Hepatocyte apoptosis; Liver fibrosis; Matrix metalloproteinase