title: Anti-atherosclerotic action of Ger-Gen-Chyn-Lian-Tang and AMPK-dependent lipid lowering effect in hepatocytes.
abstract: BACKGROUND
  The Ger-Gen-Chyn-Lian-Tang (GGCLT), an officially standardized mixture of Chinese herbal medicines, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma and Glycyrrhizae Radix in a ratio of 8:3:3:2. In this study, we evaluated the benefits of GGCLT in atherosclerotic progression.
  
  
  METHODS
  The major constituents of GGCLT were analyzed by HPLC. ApoE-/- mice taken 0.15% cholesterol diet were orally given vehicle or GGCLT (2 g/kg/day) for 12 weeks. Serum levels of lipid and glucose were analyzed, and atherosclerosis was examined by histological analyses. Cultures of vascular smooth muscle cells, hepatocytes and bone marrow-derived macrophages were used to investigate the action mechanisms of GGCLT.
  
  
  RESULTS
  Our quantitation results indicated that GGCLT contains puerarin, daidzin, daidzein, baicalin, baicalein, wogonin, palmatine, coptisine, berberine and glycyrrhizin. GGCLT decreased serum levels of total cholesterol and LDL, but not TG and HDL in ApoE-/- mice. In parallel, GGCLT treatment reduced atherosclerotic lesions and collagen expression in atheroma plaques. In vascular smooth muscle cells, GGCLT could reduce cell migration, but failed to affect cell viability and proliferation. In hepatocytes, GGCLT can reduce lipid accumulation, and this action was accompanied by the activation of AMPK, upregulation of PPARs, and downregulation of FAS. Pharmacological approach indicated that the latter two events contributing to the anti-lipogenesis is resulting from AMPK pathway, and the lipid lowering effect of GGCLT in hepatocytes is mediated by AMPK and PPARα pathways. Meanwhile, two of the major components of GGCLT, berberine and puerarin, also activated AMPK and decreased lipid accumulation in hepatocytes with berberine of higher efficacy. Besides in hepatocytes, AMPK signaling was also activated by GGCLT in vascular smooth muscle cells and macrophages.
  
  
  CONCLUSIONS
  These results demonstrate the anti-atherosclerotic action of Chinese medicine mixture GGCLT in ApoE-/- atherosclerotic mouse model. Mechanistic study suggests that activation of AMPK and PPARα in hepatocytes leading to a decrease of lipid formation contributes to the beneficial action of GGCLT in atherosclerosis treatment.
authors.affiliation: Department of Internal Medicine, Tao-Yuan General Hospital Department of Health the Executive Yuan, Taoyuan, Taiwan.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Ho
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Liao
authors.forename: Ai-Jen
authors.initials: AJ
authors.lastname: Yang
authors.forename: Pei-Dawn
authors.initials: PD
authors.lastname: Lee Chao
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
authors.forename: Chen-Tsung
authors.initials: CT
authors.lastname: Huang
authors.forename: Shu-Rung
authors.initials: SR
authors.lastname: Lin
authors.forename: Kueir-Rarn
authors.initials: KR
authors.lastname: Lee
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.forename: Wan-Wan
authors.initials: WW
authors.lastname: Lin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000089042:Coptis chinensis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006035:Glycyrrhiza; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D029908:Pueraria; D051381:Rats; D017208:Rats, Wistar; D031364:Scutellaria baicalensis
chemical_list: D001057:Apolipoproteins E; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D047492:Peroxisome Proliferator-Activated Receptors; C442842:plant extract, Puerariae Radix; C107393:Coptidis rhizoma extract; D055372:AMP-Activated Protein Kinases