基于网络药理学黄芩-黄连药对治疗2型糖尿病作用机制探讨

目的探讨黄芩-黄连药对治疗2型糖尿病(T2DM)的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索黄芩、黄连的化学成分和作用靶点,通过OMIM、TTD、Drugbank、Digsee等多个数据库查询与T2DM相关的基因。通过Uni Prot数据库查询靶点对应的基因,进而运用Cytoscape3.2.1构建化合物-靶点(基因)网络、蛋白相互作用(PPI)网络筛选出核心靶点,最后通过DAVID进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,研究其作用机制。结果化合物-靶点网络包含42个化合物和相应靶点213个,关键靶点涉及PTGS2、PTGS1、HSP90AA1、HSP90AB1、NOS2等。PPI核心网络包含15个蛋白,关键蛋白涉及TNF、IL6、INSR等。GO功能富集分析得到GO条目108个(P0.05),其中生物过程(BP)条目87个,分子功能(CC)条目9个,细胞组成(MF)条目12个。KEGG通路富集筛选得到24条信号通路(P0.05),涉及胰岛素抵抗通路、T2DM通路、胰岛素信号传递通路等。结论黄芩-黄连中的活性成分主要通过DPP4、PPARG、IL6、PPARD、TNF等靶点调节炎症细胞因子、作用于胰岛素受体协同治疗T2DM。

Mechanism of herb pair containing Scutellariae Radix and Coptidis Rhizoma on treatment of type 2 diabetes mellitus based on network pharmacology

Objective To investigate the mechanism of type 2 diabetes mellitus (T2DM) treatment by drug pair containing Scutellariae Radix and Coptidis Rhizoma. Methods The chemical composition and targets of Scutellariae Radix and Coptidis Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform (TCMSP), and T2DM related genes were searched by OMIM, TDD, Drugbank, and Digsee databases. UniProt database was used to query the target-related genes. Cytoscape 3.2.1 was used to construct compound-targets (genes) networks and protein-protein interaction (PPI) network to screen out the key targets. Finally, the mechanism of its action was studied by DAVID analyzing enrichment of gene ontology (GO) function and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG). Results The compound-target network contained 42 compounds and 213 corresponding targets, and the key targets involved PTGS2, PTGS1, HSP90AA1, HSP90AB1, NOS2, etc. The PPI core network contained 15 protein, and key protein involved in TNF, IL-6, INSR, etc. The functional enrichment analysis of GO obtained 108 GO items (P < 0.05), of which there were 87 biological processes (BP) items, 9 molecular function (CC) items, and 12 related items of cell composition (MF). There were 24 signal pathways (P < 0.05) in the KEGG pathway enrichment screening, involving insulin resistance, T2DM and insulin signaling pathway and so on. Conclusion The active components of Scutellariae Radix and Coptidis Rhizoma regulate inflammatory cytokines and act on insulin receptor in the treatment of T2DM mainly through DPP4, PPARG, IL6, PPARD, TNF, and other targets.