摘要
目的:基于网络药理学方法分析黄芪治疗免疫球蛋白A肾病(IgAN)的多成分、多靶点、多通路作用机制,为该药材的基础研究和临床应用提供依据。方法:通过GeneCards,TCMID及中药系统药理学数据库与分析平台(TCMSP)等数据库检索和文献挖掘筛选黄芪活性成分、作用靶点及与IgAN相关的疾病靶点,运用Cytoscape 3.7.1软件绘制网络图,利用网络拓扑分析黄芪治疗IgAN的关键靶点,采用R语言中的不同软件包分别进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。在此基础上,通过体外细胞实验验证黄芪中活性成分黄芪甲苷对人肾小球系膜细胞磷脂酰肌醇3-激酶/蛋白激酶B/肿瘤抑制基因p53(PI3K/Akt/p53)信号通路的激活作用。结果:筛选得到黄芪25个活性成分,49个药物-疾病共同作用靶点。GO功能富集分析包含条目84个,主要涉及细胞核激素受体结合、细胞核受体活性、脱氧核糖核酸结合转录激活因子活性等。KEGG通路富集分析包含通路88条,主要与PI3K/Akt信号通路、低氧诱导因子-1(HIF-1)信号通路、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE/RAGE)信号通路等密切相关。体外细胞实验证实,黄芪甲苷可通过调控PI3K/Akt/p53信号通路抑制重组人血小板衍生生长因子BB诱导的人肾小球系膜细胞增生。结论:黄芪多种活性成分可能通过作用于细胞凋亡、氧化应激和炎症反应等相关的靶点及通路,起到治疗IgAN的作用,为IgAN的新药开发及机制研究提供了思路。
Objective:To explore the multi-component,multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy(IgAN)by network pharmacology,aiming to provide evidence for its basic research and clinical application. Method: The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards,Traditinal Chinese Medicine Integrated Database(TCMID), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis,cell experiments in vitro were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53(PI3 K/Akt/p53) signaling pathway of human mesangial cells.Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items,which were related to nuclear hormone receptor binding,nuclear receptor activity,deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways,which were closely related to PI3 K/Akt signaling pathway,hypoxia inducible factor-1(HIF-1)signaling pathway,advanced glycation end product/receptor of advanced glycation end product(AGE/RAGE) signaling pathway and others. Cell experiments in vitro confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB(PDGF-BB)-induced proliferation of human mesangial cells by regulating PI3 K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis,oxidative stress,inflammation response and others,providing ideas and directions for the new drug development and mechanism study of IgAN.
作者
庞爽
赵栓
徐夏莲
於佳炜
丁小强
PANG Shuang;ZHAO Shuan;XU Xia-lian;YU Jia-wei;DING Xiao-qiang(Fudan University,Shanghai 200433,China;Shanghai Key Laboratory of Kidney Disease and Blood Purification,Shanghai Clinical Medical Center of Kidney Disease,Zhongshan Hospital Affiliated to Fudan University,Shanghai 200032,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第15期139-147,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
上海市肾脏疾病临床医学中心建设项目(2017ZZ01015)
复旦大学附属中山医院优秀青年人才培养计划项目(2017ZSYXQN07)。
