基于网络药理和分子对接预测复方紫银软膏治疗糖尿病足溃疡的作用靶点

Target prediction of Zi-Yin Ointment on diabetic foot ulceration based on network pharmacological analysis and molecular docking

利用网络药理和分子对接技术,探讨复方紫银软膏治疗糖尿病足溃疡的活性成分和潜在分子机制.采用中药系统药理学分析平台(TCMSP)数据库获取方中七味药的化学成分及其相关靶点.在GeneCards、OMIM、TTD、DrugBank数据库中搜集糖尿病足溃疡相关靶点,提炼出二者的交集靶点.运用Cytoscape 3.9.1软件和String数据库绘制“药物−成分−靶点−疾病”可视化网络,并筛选出核心成分和关键靶点.借助Metascape数据库对靶点进行GO和KEGG分析,运用Autodock软件以及Pymol软件进行分子对接验证和展示.结果发现,复方紫银软膏治疗糖尿病足溃疡的关键活性成分为槲皮素、绿原酸、芹菜素、山柰酚、木犀草素.从靶蛋白的角度,排名前5位的是PTGS2、HSP90AB1、PTGS1、AR、DPP4;GO富集分析提示主要包括炎症反应、细胞因子和蛋白酶受体结合等生物过程.KEGG通路主要涉及AGE-RAGE、MAPK信号通路和PI3KAkt等信号通路.分子对接结果表明复方紫银软膏中主要活性成分与关键靶点PTGS2、HSP90AB1、PTGS1、AR和DPP4具有较稳定的结合活性.复方紫银软膏治疗糖尿病足溃疡可能是多成分、多蛋白靶点、多通路的过程,为后续进一步探讨机制提供了参考依据.

The aim of this study was to investigate the active ingredients and potential molecular mechanism of Zi-Yin Ointment(ZYO)in the treatment of diabetic foot ulceration using network pharmacology and molecular docking.First,the chemical constituents and related targets of ZYO were obtained from the TCMSP database.Then,diabetic foot ulceration related targets were collected from GeneCards,OMIM,TTD,and DrugBank databases,and their intersection targets were extracted.A drug-component-target-disease visualization network was drawn using Cytoscape 3.9.1 software and the String database to screen out core components and key targets.GO and KEGG analysis were performed with the help of the Metascape database.Finally,molecular docking verification was conducted using AutoDock Vina and Pymol software.The results showed that the key active components of ZYO in the treatment of diabetic foot ulceration were quercetin,heriguard,luteolin,apigenin,kaempferol,and the first five targets were PTGS2,HSP90AB1,PTGS1,AR,and DPP4.GO enrichment analysis suggested that the biological processes mainly included inflammation response,cytokines,and protease receptor binding.KEGG pathway analysis mainly involved AGE-RAGE,MAPK,and PI3K-Akt signal pathways.Molecular docking results showed that the five main active ingredients had binding activity with the five target proteins.The treatment of diabetic foot ulceration by compound ZYO may be a multi-component,multi-protein target,and multi-pathway process,providing a reference for further study.