灵芝多糖治疗糖尿病足的网络药理学分析

Network pharmacology analysis of ganoderma lucidum polysaccharide in treating diabetic foot

目的:运用网络药理学方法研究灵芝多糖(ganoderma lucidum polysaccharide,GLP)治疗糖尿病足(diabetic foot,DF)的作用机制。方法:通过查阅文献、TCMSP、PharmMapper数据库获得GLP化学成分信息及其作用靶点。通过GeneCards和OMIM数据库检索DF相关靶点。基于在线软件Venny 2.1获得二者交集靶点。运用Cytoscape软件构建“成分-靶点-疾病”网络图。使用STRING数据库和Cytoscape软件进行蛋白互作(PPI)网络分析,根据度值筛选出核心靶点。结合DAVID数据库对核心靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)分析。结果:GLP与DF的交集靶点有98个,其中非受体酪氨酸蛋白激酶(SRC)、热休克蛋白90α编码基因(HSP90AA1)、HRas原癌基因(HRAS)、Ras同源基因家族成员A(RHOA)、丝氨酸/苏氨酸蛋白激酶(AKT1)、表皮生长因子受体(EGFR)等20个靶点可能是GLP治疗DF的关键靶点,参与癌症通路(pathways in cancer)、血管内皮生长因子(VEGF)、丝裂原活化蛋白激酶(MAPK)、脂质和动脉粥样硬化(lipid and atherosclerosis)、糖尿病并发症中的晚期糖基化终末产物及其受体(AGE-RAGE)等关键通路。结论:GLP在治疗DF方面显示出多靶点、多通路协同作用的特点,这将为中药多糖治疗糖尿病足研究提供有益的参考。

Objective:To investigate the mechanism of Ganoderma lucidum polysaccharides(GLP)in treating diabetic foot(DF)using network pharmacology methods.Methods:The chemical composition information and target points of GLP were obtained through literature review,TCMSP,and PharmMapper databases.DF-related targets were retrieved from GeneCards and OMIM databases.The intersection of the two sets of targets was obtained using the online tool Venny 2.1.A“Component-Target-Disease”network diagram was constructed using Cytoscape software.Protein-protein interaction(PPI)network analysis was conducted using STRING database and Cytoscape software,and core targets were selected based on degree values.Core targets were further analyzed for gene ontology(GO)functionality and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways using DAVID database.Results:There were 98 common targets between GLP and DF,including 20 potential key targets such as non-receptor tyrosine protein kinase(SRC),heat shock protein 90 alpha encoding gene(HSP90AA1),HRas proto-oncogene(HRAS),Ras homolog family member A(RHOA),serine/threonine protein kinase(AKT1),and epidermal growth factor receptor(EGFR).These targets may be crucial for GLP in treating DF,participating in key pathways such as Pathways in cancer,vascular endothelial growth factor(VEGF),mitogen-activated protein kinase(MAPK),lipid and atherosclerosis,and advanced glycation end-products and their receptor(AGE-RAGE)in diabetic complications.Conclusion:Ganoderma lucidum polysaccharides exhibit a characteristic of acting on multiple targets and pathways synergistically in the treatment of diabetic foot.This provides valuable reference for research on traditional Chinese medicine polysaccharide treatment of diabetic foot.