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Cyanidin‐3‐O‐β‐glucoside upregulates hepatic cholesterol 7α‐hydroxylase expression and reduces hypercholesterolemia in mice
Author(s) -
Wang Dongliang,
Xia Min,
Gao Song,
Li Dan,
Zhang Yuan,
Jin Tianru,
Ling Wenhua
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201100659
Subject(s) - liver x receptor , endocrinology , medicine , cholesterol 7 alpha hydroxylase , cholesterol , anthocyanin , glucoside , bile acid , chemistry , excretion , cyanidin , agonist , reverse cholesterol transport , biochemistry , biology , receptor , lipoprotein , food science , nuclear receptor , alternative medicine , pathology , transcription factor , gene
Scope 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 ( A po E )‐deficient mice through enhancement of fecal bile acid excretion, a critical pathway for eliminating circulation cholesterol from the body. Methods and results Five‐week‐old male A po E ‐deficient mice were fed the AIN ‐93 G 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 ( CYP 7 A 1). In mouse primary hepatocytes, cyanidin‐3‐ O ‐β‐glucoside treatment increased bile acid synthesis and CYP 7 A 1 expression in a liver X receptor alpha ( LXR α)‐)‐dependent manner. Scintillation proximity and time‐resolved fluorescence resonance energy transfer assays revealed that cyanidin‐3‐ O ‐β‐glucoside functions as an agonist of LXR α. Conclusion Our results indicate that the hypocholesterolemic activity of cyanidin‐3‐ O ‐β‐glucoside was, at least in part, mediated by activating the potential LXR α‐ CYP 7 A 1‐bile acid excretion pathway, thus contributing to the antiatherogenic effect of cyanidin‐3‐ O ‐β‐glucoside. Importantly, cyanidin‐3‐ O ‐β‐glucoside could activate LXR α in an agonist‐dependent manner.