title: Synergetic cholesterol-lowering effects of main alkaloids from Rhizoma Coptidis in HepG2 cells and hypercholesterolemia hamsters.
abstract: OBJECTIVE
  Hyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids.
  
  
  METHODS
  The cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured.
  
  
  RESULTS
  As compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation.
  
  
  CONCLUSIONS
  Our results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia.
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Shuming
authors.initials: S
authors.lastname: Kou
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Chongqing productivity promotion center for the modernization of Chinese traditional medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Chongqing productivity promotion center for the modernization of Chinese traditional medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Chongqing productivity promotion center for the modernization of Chinese traditional medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Chongqing Engineering Research Centre for Sweet Potato, School of Life Sciences, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China. Electronic address: yexiaoli@swu.edu.cn.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ye
authors.affiliation: Chongqing productivity promotion center for the modernization of Chinese traditional medicine, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China. Electronic address: xuegangli@swu.edu.cn.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D004357:Drug Synergism; D005243:Feces / Q000737:chemistry; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D012250:Rheum / Q000737:chemistry*; D014280:Triglycerides / Q000097:blood
chemical_list: D000470:Alkaloids; D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol
keywords: CYP7A1; HMGCR; Hypercholesterolemia; LDL receptor; Rhizoma Coptidis; Synergetic effect