title: Hepatoprotective effects of Ger-Gen-Chyn-Lian-Tang in thioacetamide-induced fibrosis in mice.
abstract: BACKGROUND
  Many researchers have focused on developing traditional herbal medicines as pharmacological medicines to treat hepatic fibrosis. In this study, we evaluated the possible mechanism of Ger-Gen-Chyn-Lian-Tang (GGCLT) on thioacetamide (TAA)-induced hepatic injury in mice.
  
  
  METHODS
  Hepatic fibrosis mice were established by intraperitoneal injection with TAA (100 mg/kg, 3 times/week), and treated with daily oral administration of 30 mg/kg, 100 mg/kg, and 300 mg/kg of GGCLT for 6 weeks. There were 40 mice randomly assigned to control, TAA and TAA+GGCLT groups. When the experiment was completed, Masson's trichrome staining was used to measure the degree of liver fibrosis. Hepatic fibrosis molecules were assessed by Western blot and real-time polymerase chain reaction. Hepatic glutathione levels, matrix metalloproteinase (MMP-2 and MMP-9), and hydroxyproline were also measured.
  
  
  RESULTS
  Treatment with GGCLT significantly reduced the toxicity of TAA and exhibited effective hepatoprotective activity. The mechanism of the hepatoprotective effect of GGCLT is proposed to be by normalizing oxidative stress. Additionally, the data of fibrotic areas, expression of procollagen III, and MMP2 and 9 mRNA levels in the TAA+GGCLT group were much lower than those in the TAA group (p < 0.05). Furthermore, the upregulation of hepatic protein levels of nuclear factor-κB, transforming growth factor (TGF)-β receptor-1, and smooth muscle α-actin induced by TAA was significantly inhibited after GGCLT treatment.
  
  
  CONCLUSIONS
  GGCLT can efficiently ameliorate hepatic fibrosis by its inhibitory effects on the intrahepatic oxidative stress in TAA mice model. The antioxidant properties afforded by GGCLT may be attributed to its modulation on TGF-β/TGFβ receptor signaling through the downregulation of integrated signal pathways involving smooth muscle α-actin and lipid peroxidation.
authors.affiliation: Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC; Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Chang
authors.affiliation: Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC. Electronic address: joyamen@mail.cgu.edu.tw.
authors.forename: Tzung-Yan
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC; Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Tse-Hung
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Chorng-Kai
authors.initials: CK
authors.lastname: Wen
authors.affiliation: Liver Research Unit, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Graduate Institute of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
authors.forename: Hen-Hong
authors.initials: HH
authors.lastname: Chang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D016133:Polymerase Chain Reaction; D013853:Thioacetamide
chemical_list: D004365:Drugs, Chinese Herbal; D013853:Thioacetamide
keywords: fibrosis; herbal medicines; oxidative stress