Institute for Nutrisciences and Health, National Research Council Canada, Charlottetown, PE, Canada.
Atherosclerosis. 2010 Mar;209(1):111-7. doi: 10.1016/j.atherosclerosis.2009.08.050. Epub 2009 Sep 4.
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-7alpha-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.
本研究旨在确定小檗碱（BBR）、植物甾醇（PS）及其联合应用对血浆脂质的疗效及其作用机制。雄性金黄叙利亚仓鼠随机分为 4 组（每组 15 只），给予含 0.15%胆固醇和 5%脂肪的玉米淀粉-酪蛋白-蔗糖基础饮食。3 个治疗组分别补充 0.17%（相当于 100mgkg(-1)d(-1))BBR、1%PS 或两者联合（BBRPS）4 周。研究结束时，采用酶法分析血浆脂质，采用稳定同位素示踪法分析胆固醇吸收和合成，实时 PCR 和 Western blot 分别分析肝脏和小肠中的基因和蛋白表达。BBR 和 PS 显著降低了血浆总胆固醇和非高密度脂蛋白胆固醇水平，BBRPS 与 BBR 或 PS 单独使用相比，显著改善了降脂效果。进一步研究表明，BBR 和 PS 均抑制胆固醇吸收，而增加胆固醇合成，两者联合时有协同作用。血浆总胆固醇或非高密度脂蛋白胆固醇水平与胆固醇吸收率显著相关。BBR 上调固醇 27-羟化酶基因表达，BBRPS 增加胆固醇 7α-羟化酶和固醇 27-羟化酶基因表达。BBR 和 PS 还协同降低血浆三酰甘油。这些发现表明，BBR 的降脂作用可能涉及抑制胆固醇吸收和刺激胆汁酸合成的联合作用。BBR 和 PS 的联合应用通过协同作用抑制胆固醇吸收，同时协同降低仓鼠血浆三酰甘油，从而提高降脂效果。
