基于网络药理学探究1-脱氧野尻霉素治疗2型糖尿病作用机制

The Underlying Mechanism of 1-Deoxynojirimycin for Treating Type 2 Diabetes Mellitus--A network Pharmacology Analysis

目的运用网络药理学探讨1-脱氧野尻霉素(DNJ)治疗2型糖尿病(T2DM)的潜在作用机制。方法在SwissTargetPrediction网站检索获取DNJ的潜在靶点,应用GeneCards、OMIM数据库筛选T2DM相关靶点;使用STRING11.0数据库结合Cytoscape 3.7.2软件构建靶点相互作用(PPI)网络并进行可视化,同时使用Cytoscape 3.7.2软件的Cytohubba和MCODE插件挖掘DNJ作用于T2DM的PPI网络核心靶点,最后利用Metascape数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析。结果获得DNJ与T2DM共同靶点72个,核心靶点包括MGAM、CNR1、GLA、GLB1、SI、MANBA和DRD2;GO和KEGG富集分析发现DNJ主要涉及化学突触传递、顺行突触信号、碳水化合物代谢过程等生物学过程,通过调节神经活性配体-受体相互作用、cAMP信号通路、半乳糖代谢、淀粉和蔗糖代谢等发挥T2DM治疗作用。结论DNJ可能通过多靶点、多通路发挥T2DM治疗作用。

Objective This network-pharmacology study explored the underlying mechanism of 1-deoxynojiri-mycin(DNJ)for treating type 2 diabetes mellitus(T2DM).Methods In this study,the potential targets of DNJ were predicted using SwissTargetPrediction website.The therapeutic targets of T2DM were identified by analysis of GeneCards and OMIM databases.The protein-protein interaction(PPI)network of targets was built using the STRING11.0 database,and visualized with Cytoscape 3.7.2 software.The core targets of PPI network were further identified using Cytoscape plug-ins Cytohubba and MCODE.The gene ontology(GO)and the Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed to explore the pathways related to DNJ targets in Metascape database.Results A total of 72 common targets of DNJ and T2DM were finally obtained,of which the core targets include MGAM,CNR1,GLA,GLB1,SI,MANBA,and DRD2.Furthermore,GO analysis revealed that DNJ targets were mainly involved in chemical synaptic transmission,anterograde trans-synaptic signaling,carbohydrate metabolic process and other biological processes.KEGG enrichment analysis also showed the potential role of DNJ in T2DM treatment via regulating neuroactive ligand-receptor interaction,cAMP signaling pathway,galactose metabolism,and metabolism of both starch and sucrose.Conclusion DNJ may play a potential role in T2DM treatment,involving multiple targets and their related pathways.