基于网络药理学及分子对接筛选治疗糖尿病足中药成分及相关机制研究

Screening and Mechanism Exploring of Active Compounds of Chinese Medicines for the Treatment of Diabetic Foot Based on Network Pharmacology and Molecular Docking

目的基于国家专利数据库联合网络药理学及分子对接方法,筛选治疗糖尿病足有效的中药成分,探索相关机制。方法挖掘国家专利数据库,运用IBMSPSS Modeler 18获得抗糖尿病足核心中药,从TCMSP、TCMID数据库获得核心中药的主要化学成分,通过GeneCard、TTD、OMIM、DisGeNET、DrugBank数据库查找与糖尿病足治疗相关的蛋白靶点,通过VENNY软件获取核心中药与糖尿病足的交集靶点,后对其进行GO、KEGG及PPI蛋白互作分析。借助Cytoscape软件拓扑分析后筛选出潜在的核心成分以及可能的核心靶点,最后利用Auto dock、PyMol进行对接分子能计算及可视化作图。结果筛选出潜在治疗糖尿病足核心成分5个及核心靶点6个;分子拟合计算结果显示核心靶点与核心成分稳定结合进而可通过相关信号通路发挥抗糖尿病足作用。结论槲皮素、木犀草素、山奈酚、黄芩素和β-谷甾醇等可能通过参与TNF、HIF-1等信号通路作用于AKT1、MAPK1、TNF、CASP3、TP53、PTGS2等靶点,发挥抗糖尿病足的作用。

OBJECTIVE To screen active compounds of Chinese medicine on diabetic foot and explore the mechanism based on network pharmacology and molecular docking.METHODS The national patent database was screened,and then the core Chinese medicines for diabetic foot was obtained by using IBM SPSS Modeler 18.The active chemical compounds of the core Chinese medicine were collected from TCMSP and TCMID databases,and the protein targets related to diabetic foot were obtained from GeneCard,TTD,OMIM,DisGeNET and DrugBank databases,while VENNY was used to obtain the intersection targets of active compounds and diabetic foot.Then the GO and KEGG enrichment analysis and protein interaction analysis were carried out.Cytoscape software was used to screen potential core targets and the core components.Molecular docking verification and the diagrams of docking results were done by Auto dock software and PyMOL software.RESULTS A total of 5 potential core components and 6 potential core targets for the treatment of diabetic foot were obtained.The results of molecular docking showed that the core targets were stable combined with the core components and showed a potential effect of treating diabetic foot.CONCLUSION Quercetin,luteolin,kaempferol,baicalein andβ-sitosterol show a potential effect of treating diabetic foot by acting on AKT1,MAPK1,TNF,CASP3,TP53,PTGS2 and other targets through TNF signaling pathway,HIF-1 and other related signaling pathways.