基于网络药理学研究五苓散治疗慢性肾衰竭的潜在机制

Mechanism of Wuling Powder in Treatment of Chronic Renal Failure Based on Network Pharmacology

目的:基于网络药理学方法,研究五苓散治疗慢性肾衰竭的机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索五苓散活性成分,使用有机小分子生物活性(PubChem)数据库、瑞士生物信息学研究所(SIB)数据库进行靶点排查。根据GeneCards数据库得到疾病相关靶点。并利用Omicshare平台将药物及疾病靶点进行匹配。采用String Version 10.5数据库构建靶点蛋白质-蛋白质相互作用(PPI)网络。利用Omicshare软件对关键靶点进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析。采用CytoscapeVersion3.8.0对药物-成分-靶点-信号通路进行分析。结果:筛选得到五苓散活性成分532个,治疗靶点112个,五苓散治疗疾病的主要活性成分包括啤酒甾醇(Cerevisterol),β谷甾醇(β-sitosterol),泽泻醇(Alisol B)等;治疗疾病的核心靶点包括肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)等;主要涉及的信号通路包括Toll-like Receptor(TLR)、T Cell Receptor(TCR)等,生物过程主要包括细胞凋亡过程、磷酸盐代谢过程等。结论:本研究以网络药理学方式探究了五苓散治疗慢性肾衰竭的多途径-多靶点的作用机制,推断五苓散主要通过调节TLR/NF-κB、T Cell Receptor等信号通路,抑制TNF-α、IL-6等相关炎症介质活性从而延缓慢性肾衰竭。为进一步的实验提供理论参考。

Objective:To explore the mechanism of Wuling powder in the treatment of chronic renal failure based on the network pharmacology.Methods:The main active ingredients of Wuling powder were obtained through TCMSP.SwissTargetPrediction and PubChem database were used to predict and filter the relevant action targets,and then a database of potential targets was built.Next GenCards database was used to screen reported therapeutic targets for chronic renal failure.Active components and disease targets were matched based on the Omicshare.Target protein-protein interaction(PPI)network was constructed by String Version 10.5 database.Omicshare software was used for gene ontology(GO)enrichment analysis and the Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of the key targets.Cytoscape Version 3.8.0 software was used for visualized analysis of drugs-active ingredient-key target network and the ingredient-target-signal pathway network.Results:Totally 532 active ingredients of Wuling powder and 112 targets of anti-chronic renal failure effect were screened out.The main components of Wuling powder used to treat chronic renal failure include Cerevisterol,β-sitosterol and alisol B.Core targets including TNF-αand IL-6,and receptor signaling pathways are mainly Toll-like receptor,T cell receptor signaling pathway,etc.Biological process(BP)includes regulation of programmed cell death,phosphorylation and positive regulation of cell proliferation.Conclusion:This study explored the mechanism of Wuling powder in the treatment of chronic renal failure based on the method of network pharmacology.The mechanisms of its anti-chronic renal failure effects may be related to inhibiting TNF-α、IL-6 by regulating TLR/NF-κB、T cell receptor signaling pathway.It provides theoretical reference for further experiments.