黄精干预2型糖尿病的网络药理学研究

Study on Network Pharmacology of Polygonatum for Type 2 Diabetes Intervention

目的:利用网络药理学的方法探讨黄精对2型糖尿病干预的潜在靶点。方法:通过中药系统药理学数据库与分析平台(TCMSP)筛选出黄精活性成分及潜在靶点,然后通过Gene Gards、OMIM两大数据库筛选与2型糖尿病有关的基因靶点,运用软件Cytoscape和String绘制药物-成分-靶点疾病及蛋白互相作用的网络图,利用网络拓扑分析黄精干预2型糖尿病的作用靶点,采用GO功能富集分析及KEGG通路富集分析黄精治疗2型糖尿病可能起效应的通路。结果:筛选出黄精12个药效活性成分和515个潜在作用的靶点。两大疾病基因库筛选出与2型糖尿病相关的靶点共13181个。利用网络拓扑分析最终筛选出药物和疾病共有64个靶点。GO功能富集分析得出黄精干预2型糖尿病的核心靶点主要被富集在87个信号通路,参与了细胞的代谢、增殖、信号转导、氧化应激、蛋白水解、受体激活等生物学过程;KEGG通路富集分析显示共富集在105条通路,参与癌症通路、细胞凋亡、糖尿病及并发症的AGE-RAGE信号通路、胰岛素抵抗等多种信号通路。结论:黄精干预2型糖尿病可能是AKT1、MAPK14、JUN、MTOR等多靶点效应的结果,这为临床使用黄精治疗2型糖尿提供了理论依据,同时为进一步研究作用机制提供了新的方向。

Objective:To explore the potential target of polygonatum for type 2 diabetes intervention by network pharmacology.Methods:The active components and potential targets of polygonatum were first screened by TCMSP,then Gene Gards and OMIM were used to screen gene targets related to type 2 diabetes.The network diagram of drug-component-target disease and protein interaction was drawn by using software Cytoscape and String.The target of polygonatum for intervention on type 2 diabetes was analyzed by network topology.The possible pathway of polygonatum in treating type 2 diabetes was analyzed by GO function enrichment analysis and KEGG pathway enrichment.Results:A total of 12 active components and 515 potential targets of polygonatum were screened out.A total of 13181 targets related to type 2 diabetes were screened from the two disease gene banks.Finally,64 targets of drugs and diseases were selected by network topology analysis.GO functional enrichment analysis showed that the core target of polygonatum for intervention of type 2 diabetes was mainly concentrated in 87 signal pathways,which involved in cell metabolism,proliferation,signal transduction,oxidative stress,proteolysis,receptor activation and other biological processes.KEGG pathway enrichment analysis showed that there were 105 pathways involved in cancer pathway,apoptosis,AGE-RAGE signaling pathway of diabetes and complications,insulin resistance and other signaling pathways.Conclusion:The intervention of polygonatum for type 2 diabetes may be the result of multi-target effects such as AKT1,MAPK14,JUN,MTOR,which provides a theoretical basis for clinical use of polygonatum in the treatment of type 2 diabetes,and provides a new direction for further research on the mechanism of action.