title: Epiberberine reduces serum cholesterol in diet-induced dyslipidemia Syrian golden hamsters via network pathways involving cholesterol metabolism.
abstract: This study aimed to evaluate the cholesterol-lowering effect of epiberberine in dyslipidemia Syrian golden hamsters induced by high fat and high cholesterol (HFHC) diet and its regulation mechanism on some key genes involved in cholesterol metabolism. Hamsters were divided into six groups: normal control group (NC), HFHC group, simvastatin (Sim) and three doses of epiberberine group. The body weight, organs weight and serum lipid levels, as well as total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were determined. Furthermore, the antidyslipidemia effect of epiberberine on key genes involved in cholesterol biosynthesis, uptake, conversion and elimination such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), low density lipoprotein receptor (LDL receptor), 7-alpha-hydroxylase (CYP7A1) and apical sodium dependent bile acid transporter (ASBT) were investigated. The results showed that epiberberine at high dosage significantly reduced serum TC, low density lipoprotein cholesterol (LDL-c) and TBA levels by 20.2%, 22.3% and 43.8%, respectively, and increased TBA and TC levels in feces. Epiberberine inhibited HMGCR mRNA and protein expressions and slightly reduced the protein level of ASBT, as well as dramatically up-regulated mRNA and protein expressions of CYP7A1 and LDL receptor. These findings suggested that the antidyslipidemia effects of epiberberine can be achieved via inhibiting the synthesis of cholesterol, promoting the uptake and conversion of TC in liver and increasing the excretion of TC and TBA in feces. Thus, epiberberine should be considered as one of the promising natural drugs for the treatment of dyslipidemia.
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China.
authors.forename: Zong-Yao
authors.initials: ZY
authors.lastname: Zou
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China.
authors.forename: Yin-Ran
authors.initials: YR
authors.lastname: Hu
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Ma
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China; Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control, Chongqing 400716, China; College of Environmental and Biological Engineering, Chongqing Technology and Business University, Chongqing 400067, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Chongqing Productivity Promotion Center for the Modernization of Chinese Traditional Medicine, College 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: Xue-Gang
authors.initials: XG
authors.lastname: Li
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: Xiao-Li
authors.initials: XL
authors.lastname: Ye
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D002791:Cholesterol, Dietary / Q000009:adverse effects; D006224:Cricetinae; D059305:Diet, High-Fat / Q000009:adverse effects*; D050171:Dyslipidemias / Q000097:blood* / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005243:Feces / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D011973:Receptors, LDL; D001599:Berberine; C061432:epiberberine; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase
keywords: Antidyslipidemia; Bile acids; Cholesterol metabloism; Epiberberine; Epiberberine (PubChem CID: 160876); Rhizoma Coptidis; Simvastatin (PubChem CID: 54454)