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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−1 d−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. [Copyright &y& Elsevier]

To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g/1000 kcal), without or with isoflavones (49 mg/1000 kcal) and were each fed for 6 weeks. Blood samples from 20 hyperlipidemic subjects (6M, 14F, 62±9 years, BMI 26±3 kg/m2, LDL cholesterol >160 mg/dl after feeding animal protein without isoflavones) were selected to measure TGFA fractional synthetic rate (TGFA-FSR) and free cholesterol fractional synthetic rate (FC-FSR) over 24 h as deuterium oxide uptake into TGFA and free cholesterol. Soy protein reduced TG by 12.4% (P<0.0001), total cholesterol by 4.4% (P<0.001), and LDL cholesterol by 5.7% (P=0.003) compared to animal protein. The TGFA-FSR was reduced by13.3% (P=0.018) and FC-FSR was increased by 7.6% (P=0.017) after the soy protein relative to the animal protein. Isoflavones had no significant effect on TG and TGFA-FSR. Isoflavones reduced total cholesterol levels by 3.1% (P=0.009) but had no significant effect on LDL, HDL cholesterol levels, or FC-FSR. These data demonstrate that dietary protein type modulates circulating TG and cholesterol levels in hypercholesterolemic individuals by distinct mechanisms. [Copyright &y& Elsevier]

Abstract: The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague–Dawley rats. Four groups of animals were fed a cornstarch–casein–sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100mgkg−1 bodyweightd−1), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p =0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p =0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p =0.0002) and non-HDL-C by 59% (p <0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control (p =0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p =0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects. [Copyright &y& Elsevier]