基于网络药理学与分子对接探究萸精降糖方治疗2型糖尿病的作用机制

Mechanism of Yujing Jiangtang Recipe in treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking

关键词:  萸精降糖方  2型糖尿病  网络药理学  分子对接

Key words:  Yujing Jiangtang Recipe  type 2 diabetes mellitus  network pharmacology  molecular docking

摘要:

[目的] 利用网络药理学和分子对接技术预测萸精降糖方治疗2型糖尿病（T2DM）的作用机制。[方法] 利用中药系统药理学数据库与分析平台（TCMSP）和中药分子机制生物信息分析工具（BATMAN-TCM）数据库筛选萸精降糖方的有效成分和潜在靶点。利用人类基因数据库（GeneCards）、疾病相关的基因与突变位点数据库（DisGeNET）和人类孟德尔遗传数据库（OMIM）获取2型糖尿病靶点，获得药物-疾病的共同靶点。利用STRING数据库和Cytoscape3.7.2构建靶点蛋白互作（PPI）网络。进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，并利用Cytoscape3.7.2构建“药物-有效成分-靶点-通路”的网络图。使用Auto Dock Vina 1.1.2对PPI网络图中的核心靶点和萸精降糖方的有效成分进行分子对接。[结果] 萸精降糖方治疗T2DM有88个有效成分和377个潜在靶点，311个为交集靶点。从PPI网络图中可以观察到TP53、AKT1等可能成为治疗T2DM的核心靶点。对关键靶点进行GO和KEGG富集分析发现，GO富集的生物学过程包括伤口愈合、对异生物刺激反应等；细胞组成包括膜筏、膜微区等；分子功能包括DNA结合转录因子结合、RNA聚合酶Ⅱ特异性DNA结合转录因子结合等。KEGG通路富集包括脂质与动脉粥样硬化通路、AGE-RAGE信号通路、TNF信号通路等。分子对接结果显示，槲皮素、山柰酚与核心靶点TP53、AKT1具有良好的结合活性。[结论] 研究初步探讨了萸精降糖方中有效成分在治疗T2DM方面的潜在作用机制，通过多成分、多靶点、多途径的协同作用，达到治疗T2DM的目的。

Abstract:

[Objective] To explore the possible mechanism of Yujing Jiangtang Recipe in the treatment of type 2 diabetes mellitus(T2DM) by using network pharmacology and molecular docking technology.[Methods] The TCMSP and BATMAN-TCM databases were used to screen the active ingredients and potential targets of Yujing Jiangtang Recipe. The databases GeneCards,DisGeNET and OMIM were used to obtain T2DM targets and then drug-disease common targets. Protein-Protein Interaction(PPI) network was constructed using database STRING and Cytoscape 3.7.2 software. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. were performed,and the network diagram of "drug-active ingredient-target-pathway" was constructed using Cytoscape 3.7.2 software. Auto Dock Vina 1.1.2 software was used to molecularly dock the core targets in the PPI network diagram with the active ingredients of Yujing Jiangtang Recipe.[Results] Yujing Jiangtang has 88 active ingredients and 377 potential targets in the treatment of T2DM,and 311 intersecting targets were obtained. From the PPI network diagram,TP53 and AKT1 may be the core targets for the treatment of T2DM.The GO and KEGG enrichment analyses of the key targets revealed that GO-enriched BP included wound healing,response to xenobiotic stimuli;CC included membrane rafts,membrane microregions;and MF included DNA-binding transcription factor binding,RNA polymerase Ⅱ-specific DNA-binding transcription factor binding,etc. The KEGG pathway enrichment includes lipid and atherosclerosis pathway,AGE-RAGE signalling pathway,TNF signalling pathway and so on. The molecular docking results showed that quercetin and kaempferol had good binding activities with the core targets TP53 and AKT1.[Conclusion] This study preliminarily investigated the potential mechanism of action of the active ingredients in Yujing Jiangtang Recipe in the treatment of T2DM through the synergistic effect of multiple components,multiple targets and multiple pathways.