title: Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells.
abstract: BACKGROUND
  Rhizoma coptidis (Huanglian in Chinese) is commonly used in Chinese folk medicine to treat diarrhea, diabetes, hypertension, hyperlipidemia and tumors. This herb has increasingly gained attention because of its use as a hypolipidemic herb. Berberine (BBR) is the most important constituent of R. coptidis that contribute to the pharmacological efficacy of the herb.
  
  
  OBJECTIVE
  Pharmacokinetic studies have indicated that BBR has poor oral bioavailability. Interestingly, several reports show that absorbed BBR is extensively metabolized in rats and humans. We speculate that the BBR metabolites might be responsible for the pharmacological effects. The aim of this study is to examine BBR metabolites for their triglyceride (TG)-lowering activities and the molecular mechanism to clarify BBR genuine effective forms in vivo.
  
  
  METHODS
  Four BBR metabolites were examined their TG-lowering effects with a commercial triglyceride assay kit. Real-time PCR and Western blotting were used to confirm genes and proteins of interest, respectively.
  
  
  RESULTS
  Among those BBR metabolites, M2 exhibited the more potential effects on TG-lowering and AMP-activated protein kinase (AMPK) activation in Hep G2 cells as compared with BBR. Moreover, BBR and M2 inhibited gene expressions of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), but motivated gene expression of medium chain acyl-CoA dehydrogenase (mCAD) significantly.
  
  
  CONCLUSIONS
  The results suggested that the TG-lowering effects of BBR and M2 might be partially mediated by the up-regulation of lipolysis gene expressions and down-regulation of lipogenesis gene expressions through activation of the AMPK signaling pathway. BBR and its metabolites might be in vivo active forms of oral doses of BBR, and M2 might be a promising drug candidate against hyperlipidemia.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Peixiang
authors.initials: P
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiankun
authors.initials: J
authors.lastname: Yan
authors.forename: Wen
authors.initials: W
authors.lastname: Bin
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; D000960:Hypolipidemic Agents; D014280:Triglycerides; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Berberine; Hyperlipidemia; Metabolites; Triglyceride