目的:基于网络药理学探讨"黄芪-白术-茯苓-当归"组方治疗糖尿病肾病(diabetic kidney disease,DKD)的作用机制.方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Plat-form,TCMSP)检索黄芪、白术、茯苓、当归的化学成分和作用靶点.借助OMIM数据库检索DKD的靶点,进而获取药物与疾病的交集靶点.采用Cytoscape 3.7.2 软件绘制"药物-活性成分-靶点"网络图,并筛选关键成分.利用STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并筛选核心靶点.通过Metascape数据库对交集靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析.结果:"黄芪-白术-茯苓-当归"组方的活性成分44 种,其中黄芪20 种,白术7 种,茯苓15 种,当归2 种.黄芪靶点413 个,白术靶点20 个,茯苓靶点26 个,当归靶点64 个.DKD靶点1 024 个,疾病与药物的交集靶点19 个.槲皮素、刺芒柄花素、山柰酚、异鼠李素可能是关键成分.白细胞介素(interleukin)-6、IL-10、IL-1A、IL-1β、信号传导与转录激活因子1(signal transducer and activator of transcription 1,STAT1)、C-反应蛋白(C-reactive protein,CRP)等可能是核心靶点.GO分析主要涉及血管生成调节、活性氧代谢过程、细胞因子受体结合等.KEGG通路主要包括糖尿病并发症中的AGE-RAGE信号通路、MAPK信号通路、Th17 细胞分化、JAK-STAT信号通路等.结论:"黄芪-白术-茯苓-当归"组方可能通过槲皮素、刺芒柄花素等活性成分,调控AGE-RAGE、MAPK等信号通路,作用于IL-6、IL-1A、IL-1β、STAT1、CRP等靶点,从而发挥治疗DKD的作用.
Study on the Mechanism of"Huangqi-Baizhu-Fuling-Danggui"Combination in Treating Diabetic Kidney Disease Based on Network Pharmacology
Objective:To study on the mechanism of"Huangqi(Radix Scutellariae)-Baizhu(Rhizoma Atractylodis Macrocephalae)-Ful-ing(Poria)-Danggui(Radix Angelicae Sinensis)"combination in treating diabetic kidney disease(DKD)based on network pharma-cology.Methods:The chemical components and target sites of Huangqi,Baizhu,Fuling and Danggui were retrieved from Traditional Chi-nese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database.The targets of DKD were retrieved from the Online Mendelian Inheritance in Man(OMIM)database,and the intersection of drug and disease targets was obtained.A network dia-gram of"drug-active component-target"was drawn by using Cytoscape3.7.2 software and key components were selected.The protein-protein interaction(PPI)network was constructed by using the STRING database and core targets were selected.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis on intersection targets was performed by using the Metascape data-base.Results:There were 44 active ingredients in combination of"Huangqi-Baizhu-Fuling-Danggui",of which 20 were Huangqi,7 were Baizhu,15 were Fuling,and 2 were Danggui.There were 413 targets for Huangqi,20 targets for Baizhu,26 targets for Fuling,and 64 tar-gets for Danggui.There were 1 024 DKD targets and 19 intersection targets between diseases and drugs.Quercetin,Formaronetin,Kaempferol,and Isorhamnetin might be key components.Interleukin-6,IL-10,IL-1A,IL-1β,signal transduction and activator of tran-scription 1(STAT1)and C-reactive protein(CRP)might be core targets.GO analysis mainly involved regulation of angiogenesis,reac-tive oxygen species metabolic processes,and cytokine receptor binding.KEGG pathway mainly included AGE-RAGE signaling pathway in diabetes complications,MAPK signaling pathway,Th17 cell differentiation,JAK-STAT signaling pathway,etc.Conclusion:The combi-nation of"Huangqi-Baizhu-Fuling-Danggui"may regulate the AGE-RAGE,MAPK and other signaling pathways through active compo-nents,such as quercetin and anthocyanin,and act on targets,such as IL-6 and IL-10,thereby exerting a therapeutic effect on DKD.
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