title: The safety and anti-hypercholesterolemic effect of coptisine in Syrian golden hamsters.
abstract: Current work was conducted to evaluate the cholesterol-lowering effect of coptisine extracted from Rhizoma coptidis in Syrian golden hamsters. The safety results indicated that coptisine was a safe and low-toxic compound. Coptisine showed a beneficial effect in the abnormal serum lipid levels induced by a high-fat and high-cholesterol diet (HFHC): at a concentration of 70.05 mg/kg, coptisine significantly led to a decrease in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-c) levels by 26.70, 15.38, and 22.22 %, respectively, and high-density lipoprotein cholesterol (HDL-c) was increased by 41.74 % in serum of hamsters (p < 0.01). In addition, total bile acid (TBA) levels in feces of hamsters were elevated after coptisine administration. Further investigation has suggested that the mRNA and protein expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) in the liver of hamsters was down-regulated by high-dosage coptisine treatment (p < 0.05); mRNA and protein expression of low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) were dramatically up-regulated by coptisine administration. The apical sodium-dependent bile salt transporter expression was down-regulated in the coptisine-treated animals, but showed no significant differences from the HFHC groups. Taken together, our results demonstrate that a high dosage of coptisine could inhibit cholesterol synthesis via suppressing the HMGCR expression and promoting the use and excretion of cholesterol via up-regulating LDLR and CYP7A1 expression. These findings suggest a critical role for coptisine in anti- hypercholesterolemia, and thus it needs to be considered as a potential natural cholesterol lowering agent.
authors.affiliation: School of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
authors.forename: Kai
authors.initials: K
authors.lastname: He
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ye
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: YanZhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zongyao
authors.initials: Z
authors.lastname: Zou
authors.forename: Na
authors.initials: N
authors.lastname: Ning
authors.forename: Yinran
authors.initials: Y
authors.lastname: Hu
authors.forename: Biao
authors.initials: B
authors.lastname: Chen
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fang
authors.forename: Xuegang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001599:Berberine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood*; D006224:Cricetinae; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D012333:RNA, Messenger / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D014280:Triglycerides; C034384:coptisine; D001599:Berberine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases