title: Chlorogenic acid-enriched extract from Eucommia ulmoides leaves inhibits hepatic lipid accumulation through regulation of cholesterol metabolism in HepG2 cells.
abstract: BACKGROUND
  Eucommia ulmoides Oliver (Eucommiaceae) leaf exhibits beneficial lipid-lowering and anti-obesity effects. However, the mechanisms remain unknown.
  
  
  OBJECTIVE
  The objective of this study is to investigate the lipid-lowering effects of chlorogenic acid (CGA)-enriched extract from this plant (CAEF) in human hepatoma HepG2 cells, focusing on cholesterol metabolism.
  
  
  METHODS
  HepG2 cells were treated with CAEF (10, 20, 25, 40, 60, and 80 mg/L), CGA (0.3, 3, 30, 300, and 600 μmol/L), and simvastatin (0.1, 1, 10, 50, and 100 μmol/L) for 24 or 48 h. The cytotoxicity, Oil red O staining, total cholesterol, and triacylglycerol in supernatants were determined. The mRNA expression of genes involved in cholesterol metabolism was determined with RT-PCR. The protein expression of HMG-CoA reductase (HMGCR) was examined by immunocytochemistry and western-blot.
  
  
  RESULTS
  The IC50 values were 59.2 mg/L for CAEF, 335.9 μmol/L for CGA, and 10.5 μmol/L for simvastatin. By treating cells with CAEF (25 mg/L), CGA (30 μmol/L), or simvastatin (10 μmol/L) for 48 h, the efflux of total cholesterol and triacylglycerol was increased (CAEF, 4.06- and 31.00-folds; CGA, 2.94- and 2.17-folds; and simvastatin, 3.94- and 24.67-folds), and the cellular lipid droplets were reduced in Oil red O staining. CAEF and CGA increased mRNA expression of ABCA1, CYP7A1, and AMPKα2, while CAEF and simvastatin decreased SREBP2. However, their effects on LXRα mRNA expression were variable. Importantly, all drugs significantly inhibited protein expression of HMGCR at mRNA and protein levels.
  
  
  CONCLUSIONS
  CAEF is a promising dietary supplement to prevent obesity and dyslipidemia and the effects appear to be due, at least in part, to regulating cholesterol metabolism through inhibition of HMGCR in HepG2 cells.
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Shun
authors.initials: S
authors.lastname: Hao
authors.affiliation: b Pharmaceutical Preparation Section, Guizhou Province People's Hospital , Guiyang , Guizhou , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Mo
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Peng
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Canhui
authors.initials: C
authors.lastname: Xiang
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Zunyi Medical University, Zhuhai Campus , Zhuhai , Guangdong , China and.
authors.forename: Wenna
authors.initials: W
authors.lastname: Li
mesh_terms: D002726:Chlorogenic Acid / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D031283:Eucommiaceae / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry
chemical_list: D004365:Drugs, Chinese Herbal; D002726:Chlorogenic Acid; D002784:Cholesterol
keywords: ABCA1; AMPKα; CYP7A1; HMGCR; SREBP2; chlorogenic acid; lipid accumulation