Metabolic profile associated with glucose and cholesterol lowering effects of berberine in Sprague-Dawley rats

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.