基于网络药理学的葛根芩连汤治疗2型糖尿病的效应机制

Effective Mechanism of Gegen Qinlian Tang in Treating Type 2 Diabetes Mellitus Based on Network Pharmacology

目的：运用网络药理学分析方法探究葛根芩连汤（Gegen Qinliantang,GQT）治疗2型糖尿病（type 2 diabetes mellitus,T2DM）的潜在效应机制。方法：利用整合药理学平台（Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine,TCMIP）收集GQD中4味中药的化学成分及T2DM的相关靶点基因,并根据二维结构相似性特征筛选药物靶标;采用整合药理学平台在线Cytoscape技术构建核心靶标网络及＂中药-成分-靶标-通路＂多维网络;利用平台基因功能注释（Gene Ontology,GO）和京都基因和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes,KEGG）对核心靶标进行基因功能和通路的注释分析。结果：共收集葛根芩连汤234种成分,核心靶标175个;其中筛选得到的68个活性成分与蛋白激酶C-δ（PRKCD）,葡萄糖激酶（GCK）,细胞色素C氧化酶亚基（COX7C/COX5A/COX5B）,ATP合成酶F1亚基（ATP5F1A/ATP5F1C）,胰岛素受体（INSR）等22个主要蛋白具有强相互作用,主要涉及在内分泌系统,细胞生长与死亡,Fox O转录因子（Fox O）信号通路,脂肪细胞因子信号通路,胰岛素信号通路等多条通路。结论：本研究初步揭示了葛根芩连汤治疗2型糖尿病的效应机制,其机制多与抗炎、抗氧化应激、抗胰岛β细胞损伤、改善糖脂代谢和并发症等相关。

Objective： To explore the potential mechanism of Gegen Qinlian Tang（ GQT） in the treatment of type 2 diabetes mellitus（ T2 DM） using network pharmacology. Method： Four chemical components of GQT and target genes of T2 DM were collected in Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine（ TCMIP）. The drug targets were screened out according to the Similarity of Two-Dimensional structures. The online Cytoscape technology in TCMIP was used to build the core target network and ＂herbsingredient-target-pathway＂network. Gene Ontology（ GO） gene function combined with Kyoto Encyclopedia of Genes and Genomes（ KEGG） pathway enrichment module was used to annotate and analyze the gene function and signaling pathway of the core target. Result： Based on the TCMIP,234 chemical components of GQT and 175 core targets were collected. Multi-dimensional network analysis showed that 68 active components had strong interactions with protein kinase C-δ（ PRKCD）,glucokinase（ GCK）,cytochrome C oxidase subunit（ COX7 C/COX5 A/COX5 B）,ATP synthase F1 subunit（ ATP5 F1 A/ATP5 F1 C）,insulin receptor（ INSRS） and other 22 major proteins; the biological pathways mainly involved in the endocrine system,cell growth and death,Fox O signaling pathway,adipocytokine signaling pathway, insulin signaling pathway and so on. Conclusion： The findings preliminarily reveal the effective mechanism of GQT in treating T2 DM,which is related to anti-inflammation,antioxidation stress,anti-insulin β cell injury,and improvement of glycolipid metabolism and complications.