基于网络药理学研究孜亚比提片对2型糖尿病的潜在分子机制

Study on the potential molecular mechanism of Ziyabiti tablets on type 2 diabetes based on network pharmacology

目的 利用网络药理学方法研究孜亚比提片治疗2型糖尿病(T2DM)的分子机制。方法 从TCMSP、ETCM、CNKI中得到孜亚比提片化学成分和药物靶点,利用OMIM和GeneCards数据库筛选T2DM的疾病靶点;使用Cytoscape 3.6.1软件构建“药物-成分-靶点网络”筛选出核心成分;运用蛋白质相互作用网络筛选出核心靶点;通过DAVID数据库进行GO和KEGG富集分析。结果研究共收集到孜亚比提片活性成分144个,度值排名靠前的为槲皮素、山柰酚、异鼠李素等。活性成分相关靶点823个,其中与T2DM相关的有700个,包含为SRC、MAPK1、MAPK3等。GO功能分析提示与信号传导、蛋白质磷酸化以及蛋白质结合等分子功能有关。KEGG通路富集分析所涉及的主要信号通路有脂质与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路及HIF-1信号通路等。结论 孜亚比提片治疗T2DM具有多成分、多靶点、多通路协同干预的特点,其主要由槲皮素、山柰酚、异鼠李素等成分通过作用SRC、MAPK1、MAPK3靶点调控AGE-RAGE信号通路发挥综合治疗作用。

Objective To study the molecular mechanism of Ziyabiti tablets in the treatment of type 2 diabetes(T2DM) by network pharmacology.Methods The chemical components and related targets of Ziyabiti tablets were obtained from TCMSP,ETCM and CNKI,and the targets of T2DM were screened by OMIM and GeneCards databases.The "drugcomponent-target" network was built by Cytoscape 3.6.1 to screen out the core components and the core targets were screened by protein-protein interaction network.GO functional analysis and KEGG pathway enrichment analysis were performed by DAVID database.Results A total of 144 active components of Ziyabiti tablets were collected in this study,and quercetin,kaempferol,isorhamnetin and so on with higher degree values.There were 823 related targets,of which 700 were related to T2DM,including SRC,MAPK1,MAPK3,etc.GO function analysis suggested that it was related to molecular functions such as signal transduction,protein phosphorylation and protein binding.The main signaling pathways involved in KEGG pathway enrichment analysis were AGE-RAGE signaling pathways in lipid and atherosclerosis,prostate cancer,and diabetic complications.Conclusion Ziyabiti tablets have the characteristics of multicomponent,multi-target,and multi-pathway synergistic intervention in the treatment of T2DM,which is mainly composed of quercetin,kaempferol,isorhamnetin and other components to regulate AGE-RAGE signaling pathways through SRC,MAPK1,MAPK3 targets.