Based on network pharmacology to explore the molecular mechanisms of astragalus membranaceus for treating T2 diabetes mellitus
Based on network pharmacology to explore the molecular mechanisms of astragalus membranaceus for treating T2 diabetes mellitus
复制标题
基于网络药理学探讨黄芪治疗T2糖尿病的分子机制
DOI：
10.21037/atm.2019.10.118
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发表时间：
2019-11-01
影响因子：
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通讯作者：
Xu, Yunsheng
中科院分区：
文献类型：
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作者：
Li, Jie;Huang, Yanqin;Xu, Yunsheng
背景：黄芪是一种用于治疗2型糖尿病（T2DM）的中药，但其分子机制尚不清楚。本研究通过网络药理学分析黄芪抗T2DM的分子机制。方法：首先找到黄芪与疾病的共同靶点，利用String构建蛋白质-蛋白质相互作用（PPI）网络，然后通过拓扑分析从这些共同靶点中筛选关键靶点。随后，将共同靶点引入DAVID中，实现基因本体（GO）和KEGG富集分析的结果。观察黄芪的治疗效果，并通过动物实验验证了几个关键靶点。结果：首先，通过拓扑分析发现了13个关键靶点（EGFR、KDR、SRC、ERBB2、FYN、ESR1、AR、HSP90AA1、PTGS2、ABCG2、AB1、MMP2、CYP1）。然后，GO和KEGG的结果提示，黄芪的抗糖尿病作用与受体蛋白酪氨酸激酶（RPTK）的激活密切相关。动物实验结果表明，黄芪能增强大鼠胰腺形态，上调酪氨酸受体表达。结论：总之，本研究发现了13个关键靶点，发现黄芪通过提高酪蛋白激酶活性、调节脂质代谢、增强胰岛素抵抗等上调胰岛素信号通路来治疗T2DM。本研究为后续实验研究奠定了基础，拓宽了黄芪的临床应用。
Background: Astragalus membranaceus refers to a type of traditional Chinese medicine (TCM) used to treat type 2 diabetes mellitus (T2DM), whereas its molecular mechanism remains unclear. In the presented study, network pharmacology was performed to analyze the molecular mechanism of astragalus membranaceus against T2DM.Methods: First, we found common targets of astragalus membranaceus and disease, protein-protein interaction (PPI) network was built by String, and then key targets were screened from these common targets by topological analysis. Subsequently, common targets were introduced into DAVID to achieve the results of gene ontology (GO) and KEGG enrichment analysis. The therapeutic effect of astragalus was observed, and several key targets were verified by an animal experiment.Results: First, 13 key targets (EGFR, KDR, SRC, ERBB2, FYN, ESR1, AR, HSP90AA1, PTGS2, ABCG2, AB1, MMP2, and CYP1) were found by topological analysis. Then, the results of GO and KEGG suggested that the anti-diabetes effect of astragalus membranaceus was strongly associated with the activation of receptor protein tyrosine kinase (RPTK). The results of animal experiments revealed that astragalus could enhance the morphology of rat pancreas and up-regulate the expression of tyrosine receptor.Conclusions: In brief, 13 key targets were found in this study, and astragalus membranaceus was found up-regulating insulin signaling pathways by improving the activity of casein kinase, regulating lipid metabolism, and enhancing insulin resistance to treat T2DM. The present study lays a basis for subsequent experimental research and broadens the clinical application of astragalus membranaceus.