Metabolic profile associated with glucose and cholesterol lowering effects of berberine in Sprague-Dawley rats
Metabolic profile associated with glucose and cholesterol lowering effects of berberine in Sprague-Dawley rats
复制标题
DOI：
10.1007/s11306-012-0407-7
复制
发表时间：
2012-12-01
期刊：
影响因子：
3.6
通讯作者：
Li, Sam Fong Yau
中科院分区：
文献类型：
--
作者：
Jiang, Zhangjian;Liu, Feng;Li, Sam Fong Yau
在这项研究中，我们提出了一个综合的策略，去卷积的代谢特征与小檗碱降低胆固醇的影响，在Sprague-Dawley大鼠的肝脏。大鼠给予小檗碱50 mg/kg。采集尿样和肝组织用于代谢物含量分析，同时采集肝脏和肾脏用于组织病理学检查。采用气相色谱/质谱联用技术分析肝脏中脂肪酸、胆固醇、葡萄糖等代谢物。使用液相色谱/串联质谱法进行靶向分析，并使用质子核磁共振（H-1 NMR）进行非靶向分析，对尿液代谢物进行分析。我们的研究结果表明，使用液相色谱/质谱（LC/MS）和H-1 NMR分析大鼠尿样中的代谢物产生互补的，一致的和可靠的结果。小檗碱的给药导致大鼠肝脏样品中葡萄糖、麦芽糖、脂肪酸（饱和和不饱和）和胆固醇的减少。不同日期的尿代谢谱分析表明，在大鼠肝脏胆固醇降低之前，发现高碳水化合物使用率是早期事件（第2天）。结果表明，这些动物通过改变氨基酸和脂肪酸的合成和消耗来利用替代能源。此外，第2天给药动物的谷氨酰胺水平变化表明谷氨酰胺和谷氨酸代谢可能受到影响。由于谷氨酰胺是核苷酸合成的前体，并且核苷酸是细胞生长和复制所需的，因此结果与观察到的胆固醇降低作用和体重减轻一致。最后，我们的研究结果表明，LC/MS和H-1 NMR的组合提供了一个独特的代谢谱与小檗碱在大鼠肝脏中的降胆固醇作用。
In this study, we present an integrated strategy to deconvolute the metabolic signatures associated with the cholesterol lowering effect of berberine in the livers of Sprague-Dawley rats. The rats were dosed with berberine at 50 mg/kg. Urine samples and liver tissues were collected for the analysis of metabolite contents, while livers and kidneys were collected for histopathology. Metabolites such as fatty acids, cholesterol, glucose and others in liver were analyzed by gas chromatography/mass spectrometry. The urinary metabolites were analyzed using targeted profiling with liquid chromatography/tandem mass spectrometry and non-targeted profiling with proton nuclear magnetic resonance (H-1 NMR). Our results demonstrated that analysis of metabolites in rat urine samples using liquid chromatography/mass spectrometry (LC/MS) and H-1 NMR produced complementary, consistent and reliable results. The administration of berberine resulted in a reduction of glucose, maltose, fatty acids (saturated and unsaturated) and cholesterol in the rat liver samples. The analysis of urinary metabolic profiles on different days showed that before the cholesterol reduction in the rat livers, a high rate of carbohydrate usage was found to be an early event (day 2). The results suggested that the animals utilized alternative energy sources by altering the synthesis and consumption of amino acids and fatty acids. In addition, changes in the level of glutamine for the treated animals on day 2 suggested that glutamine and glutamate metabolism could be affected. Since glutamine is a precursor for nucleotides synthesis and nucleotides are required for cell growth and replication, the results are consistent with the observed cholesterol lowering effect and weight reduction. Finally, our results demonstrated that the combination of LC/MS and H-1 NMR provided a unique metabolic profile associated with the cholesterol lowering effect of berberine in rat livers.