title: Cyanidin-3-O-β-glucoside upregulates hepatic cholesterol 7α-hydroxylase expression and reduces hypercholesterolemia in mice.
abstract: METHODS
  Although previous studies have shown that consumption of anthocyanin extract from plant foods reduces hypercholesterolemia and the severity of atherosclerosis in different animal models, the mechanisms of these actions remained unclear. This study investigated whether pure anthocyanin inhibit atherosclerosis development and reduce hypercholesterolemia in the apolipoprotein E (ApoE)-deficient mice through enhancement of fecal bile acid excretion, a critical pathway for eliminating circulation cholesterol from the body.
  
  
  RESULTS
  Five-week-old male ApoE-deficient mice were fed the AIN-93G diet supplemented with or without cyanidin-3-O-β-glucoside (0.06% w/w) for 12 weeks. Results showed that cyanidin-3-O-β-glucoside consumption inhibited the formation of aortic sinus plaque and reduced hypercholesterolemia, along with promoted fecal bile acid excretion and upregulated hepatic cholesterol 7a-hydroxylase expression (CYP7A1). In mouse primary hepatocytes, cyanidin-3-O-β-glucoside treatment increased bile acid synthesis and CYP7A1 expression in a liver X receptor alpha (LXRα)-)-dependent manner. Scintillation proximity and time-resolved fluorescence resonance energy transfer assays revealed that cyanidin-3-O-β-glucoside functions as an agonist of LXRα.
  
  
  CONCLUSIONS
  Our results indicate that the hypocholesterolemic activity of cyanidin-3-O-β-glucoside was, at least in part, mediated by activating the potential LXRα-CYP7A1-bile acid excretion pathway, thus contributing to the antiatherogenic effect of cyanidin-3-O-β-glucoside. Importantly, cyanidin-3-O-β-glucoside could activate LXRα in an agonist-dependent manner.
authors.affiliation: Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, P R China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tianru
authors.initials: T
authors.lastname: Jin
authors.forename: Wenhua
authors.initials: W
authors.lastname: Ling
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy*; D001647:Bile Acids and Salts / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005960:Glucosides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000872:Anthocyanins; D001057:Apolipoproteins E; D001647:Bile Acids and Salts; D005960:Glucosides; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; C462279:cyanidin-3-O-beta-glucopyranoside; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse