Berberine and plant stanols synergistically inhibit cholesterol absorption in hamsters

Abstract 

The present study was conducted to determine the efficacy and underlying mechanism of berberine (BBR), plant stanols (PS) and their combination on plasma lipids. Male Golden Syrian hamsters were randomly divided into 4 groups (n=15/group) and fed a cornstarch–casein–sucrose-based diet containing 0.15% cholesterol and 5% fat. Three treatment groups were supplemented with 0.17% (equivalent to 100mgkg⁻¹d⁻¹) BBR, 1% PS, or a combination of both (BBRPS) for 4wk. At the end of the study, plasma lipids were analyzed with enzymatic methods, cholesterol absorption and synthesis using stable isotope tracer methodology, and gene and protein expressions in the liver and small intestine using real-time PCR and Western blot, respectively. BBR and PS significantly lowered plasma total- and nonHDL-cholesterol levels, and BBRPS markedly improved cholesterol-lowering efficacy compared to BBR or PS alone. Further examinations revealed that BBR and PS both inhibited cholesterol absorption and by contrast, increased cholesterol synthesis, and exerted a synergistic action when they were combined. Plasma total or nonHDL-cholesterol levels were significantly correlated with cholesterol absorption rates. BBR upregulated sterol 27-hydroxlase gene expression and BBRPS increased both cholesterol-7α-hydroxylase and sterol 27-hydroxlase gene expressions. BBR and PS also synergistically decreased plasma triacylglycerides. These findings suggest that the cholesterol-lowering action of BBR might involve a combination of inhibition of cholesterol absorption and stimulation of bile acid synthesis. The combination of BBR and PS improves cholesterol-lowering efficacy through a synergistic action on cholesterol absorption, in addition to synergistically reducing plasma triacylglycerols in hamsters.

Abbreviations: ABCG, ATP-binding cassette superfamily G, BBR, berberine chloride, BBRPS, combination of BBR and plant stanols, BW, body weight, CT, control, FSR, free cholesterol fractional synthesis rate, CYP7A1, cholesterol-7α-hydroxylase, CYP27A1, sterol 27-hydroxlase, GAPDH, glyceraldehyde 3-phosphate dehydrogenase, GC, gas chromatography, GC/C/IRMS, gas chromatography/combustion/isotope ratio mass spectrometer, GC/P/IRMS, gas chromatography/pyrolysis/isotope ratio mass spectrometer, HDL-C, HDL-cholesterol, IRMS, isotope ratio mass spectrometer, LDL-C, LDL-cholesterol, LDLR, LDL-receptor, nonHDL-C, nonHDL-cholesterol (very low density lipoprotein cholesterol+intermediate density lipoprotein cholesterol+LDL-cholesterol), NPC1L1, Niemann-Pick C1 Like 1, PS, plant stanols, TAG, triacylglycerol, T-C, total cholesterol

Keywords: Berberine, Plant stanols, Plasma lipids, Cholesterol absorption, Cholesterol synthesis, LDL-receptor, Hamster