Key Laboratory of Digital Quality Evaluation of Chinese Materia Medical of State Administration of TCM, China.
Engineering & Technology Research Centre for Chinese Materia Medical Quality of Guangdong Province, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Oxid Med Cell Longev. 2020 May 27;2020:1805418. doi: 10.1155/2020/1805418. eCollection 2020.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease. (), also named Kushen, is a famous Chinese herbal medicine that has been used to prevent and cure T2DM both in folk medicine and in medical institution. However, its mechanism of action remains unclear. In this study, the pharmacodynamic effects of EtOAc extract (SFE) on high-fat diet and low-dose streptozotocin-induced T2DM rats were examined. Fecal metabolomics analysis and 16S rRNA gene sequencing were applied to determine the influence of T2DM and SFE treatment on gut microbiota and host metabolism. Based on the consistency of the results of metabolic pathways in metabolomics analysis and phylogenetic investigation of communities by reconstruction of unobserved state (PICRUSt) analysis of 16S rRNA gene sequencing, the level of metabolites and the operational taxonomic units of gut bacteria were combined, and Spearman's analysis was implemented. Our data showed that SFE significantly decreased fasted blood glucose levels and improved lipid profile, glycosylated serum protein, glycosylated hemoglobin index, and pancreas damage. Metabolomics and 16S rRNA gene sequencing analysis indicated gut bacteria disorder, disturbed lipid metabolism, carbohydrate metabolism, and especially amino acid metabolism in T2DM and that SFE can regulated these metabolic pathways through the influence on gut bacteria. Spearman's analysis indicated that the amino acid metabolism that included tryptophan, branched chain amino acid, aromatic amino acid, beta-alanine, and glycine, serine and threonine metabolism, lipid metabolism, including lysophosphatidylcholines and lysophosphatidylethanolamines, primary bile acid and linoleic acid metabolism, carbohydrate metabolism, and nucleotide metabolism positively correlated with , , , , , and . In addition, arginine and proline metabolism, steroid hormone, steroid biosynthesis, and sphingolipid metabolism positively correlated with , , , , and . Taken together, we speculated that SFE may have an effect on T2DM by mediating host-microbial metabolic axis. Exploration of SFE treatment for T2DM by multiomics is expected to provide a reference for clinical treatment.
2 型糖尿病(T2DM)是一种慢性代谢性疾病。苦参是一种著名的中草药,在民间医学和医疗机构中都被用于预防和治疗 T2DM。然而,其作用机制尚不清楚。在这项研究中,考察了 EtOAc 提取物(SFE)对高脂肪饮食和低剂量链脲佐菌素诱导的 T2DM 大鼠的药效作用。应用粪便代谢组学分析和 16S rRNA 基因测序来确定 T2DM 和 SFE 治疗对肠道微生物群和宿主代谢的影响。基于代谢组学分析中代谢途径的结果和 16S rRNA 基因测序的重建未观察状态的群落系统发育分析(PICRUSt)的一致性,将代谢物水平和肠道细菌的操作分类单位结合起来,并进行 Spearman 分析。我们的数据表明,SFE 可显著降低空腹血糖水平,改善血脂谱、糖化血清蛋白、糖化血红蛋白指数和胰腺损伤。代谢组学和 16S rRNA 基因测序分析表明,T2DM 存在肠道细菌紊乱、脂质代谢、碳水化合物代谢,特别是氨基酸代谢紊乱,而 SFE 可以通过影响肠道细菌来调节这些代谢途径。Spearman 分析表明,包括色氨酸、支链氨基酸、芳香族氨基酸、β-丙氨酸和甘氨酸、丝氨酸和苏氨酸代谢、脂质代谢(包括溶血磷脂酰胆碱和溶血磷脂酰乙醇胺、初级胆汁酸和亚油酸)、碳水化合物代谢和核苷酸代谢与 、 、 、 、 呈正相关。此外,精氨酸和脯氨酸代谢、甾体激素、甾体生物合成和鞘脂代谢与 、 、 、 、 呈正相关。综上所述,我们推测 SFE 通过调节宿主-微生物代谢轴可能对 T2DM 有作用。通过多组学探索 SFE 治疗 T2DM,有望为临床治疗提供参考。
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