title: The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells.
abstract: BACKGROUND
  Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation.
  
  
  METHODS
  The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay.
  
  
  RESULTS
  Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells.
  
  
  CONCLUSIONS
  These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
authors.forename: Seolah
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
authors.forename: Jeongjun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
authors.forename: Hyunghee
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
authors.forename: Haerim
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
authors.forename: Jonghoon
authors.initials: J
authors.lastname: Lim
authors.affiliation: Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Heejeong
authors.initials: H
authors.lastname: Yang
authors.affiliation: Formula Sciences, College of Oriental Medicine, Dongeui University, Busan 47340, Korea. Electronic address: ssshin@deu.ac.kr.
authors.forename: Soon Shik
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea. Electronic address: yoon60@mokwon.ac.kr.
authors.forename: Michung
authors.initials: M
authors.lastname: Yoon
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056945:Hep G2 Cells; D006505:Hepatitis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D009765:Obesity / Q000235:genetics; D010080:Oxazoles / Q000494:pharmacology; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020334:Rats, Inbred OLETF; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; C449302:GW 6471; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D008055:Lipids; D010080:Oxazoles; D047493:PPAR alpha; D010936:Plant Extracts; D012333:RNA, Messenger; C000607504:gambigyeongsinhwan; D014443:Tyrosine; D000410:Alanine Transaminase; D011345:Fenofibrate
keywords: Alnus japonica; Curcuma longa; Fatty acid oxidation; Lipogenesis; Massa Medicata Fermentata; Peroxisome proliferator-activated receptor α