Berberine decreases cholesterol levels in rats through multiple mechanisms, including inhibition of cholesterol absorption

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DOIResolve DOI: http://doi.org/10.1016/j.metabol.2014.05.013
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TypeArticle
Journal titleMetabolism: Clinical and Experimental
ISSN0026-0495
Volume63
Issue9
Pages11671177; # of pages: 11
SubjectAcyl-coenzyme A:cholesterol acyltransferase-2; Berberine; Cholesterol absorption; Cholesterol micellarization; Rat; Anticholesteremic Agents; Caco-2 Cells; Cell Membrane Permeability; Cholesterol; Diet, Atherogenic; Dietary Supplements; Enterocytes; Gene Expression Regulation, Enzymologic; Hypercholesterolemia; Intestinal Absorption; Micelles; Random Allocation; Rats, Sprague-Dawley; Sterol O-Acyltransferase
AbstractObjective The objective was to determine the mechanisms of action of berberine (BBR) on cholesterol homeostasis using in vivo and in vitro models. Methods Male Sprague-Dawley rats were fed the AIN-93G diet (normal control) or modified AIN-93G diet containing 28% fat, 2% cholesterol and 0.5% cholic acid with treatment of 0 (atherogenic control), 50, 100, and 150 mg/kg·d of BBR, respectively by gavaging in water for 8 weeks. Cholesterol absorption rate was measured with the dual stable isotope ratio method, and plasma lipids were determined using the enzymatic methods. Gene and protein expressions of Acyl-coenzyme A:cholesterol acyltransferase-2 were analyzed in vivo and in vitro. Cholesterol micellarization, uptake and permeability were determined in vitro. Results Rats on the atherogenic diet showed significantly hypercholesterolemic characteristics compared to normal control rats. Treatment with BBR in rats on the atherogenic diet reduced plasma total cholesterol and nonHDL cholesterol levels by 29%-33% and 31%-41%, respectively, with no significant differences being observed among the three doses. The fractional dietary cholesterol absorption rate was decreased by 40%-51%. Rats fed the atherogenic diet showed lower plasma triacylglycerol levels, and no changes were observed after the BBR treatment. BBR interfered with cholesterol micellarization, decreased cholesterol uptake by Caco-2 cells and permeability through Caco-2 monolayer. BBR also inhibited the gene and protein expressions of acyl-coenzyme A cholesterol acyltransferease-2 in the small intestine and Caco-2 cells. Conclusion BBR lowered blood cholesterol levels at least in part through inhibiting the intestinal absorption and further by interfering with intraluminal cholesterol micellarization and decreasing enterocyte cholesterol uptake and secretion.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Aquatic and Crop Resource Development; NRC Institute for Nutrisciences and Health
Peer reviewedYes
NPARC number21272711
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Record identifiere96c423c-3e8b-42d2-bf28-8a44e14a732c
Record created2014-12-03
Record modified2016-05-09
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