基于网络药理学探讨柴胡-黄芩治疗慢性肾功能衰竭的作用机制

Study on the Action Mechanism of Chaihu-Huangqin in Treating Chronic Renal Failure Based on Network Pharmacology

目的:基于网络药理学探讨柴胡-黄芩治疗慢性肾功能衰竭(chronic renal failure, CRF)的作用机制。方法:基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)检索柴胡、黄芩的活性成分及其相关靶点。通过在线人类孟德尔遗传数据库(online mendelian inheritance in man, OMIM)和GeneCards数据库检索CRF相关靶点。应用Draw Venn Diagram在线工具将柴胡、黄芩活性成分相关靶点与CRF相关靶点取交集并绘制韦恩图,得到的交集靶点即柴胡-黄芩治疗CRF的潜在靶点,采用Cytoscape3.8.0软件构建“活性成分-潜在靶点”网络图。采用STRING11.0数据库构建潜在靶点蛋白质相互作用(protein-protein interaction, PPI)网络,并筛选柴胡-黄芩治疗CRF的核心靶点。将潜在靶点导入Metascape平台进行基因本体(gene ontology, GO)功能富集分析中的生物学过程(biological process, BP)分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析,并采用Cytoscape 3.8.0软件构建“潜在靶点-信号通路”网络图。结果:基于TCMSP得到柴胡活性成分13种、黄芩活性成分32种及216个相关靶点。从GeneCards数据库及OMIM数据库获得CRF相关靶点2 607个,活性成分相关靶点与CRF相关靶点进行映射,得到137个柴胡-黄芩治疗CRF的潜在作用靶点。PPI网络分析得到6个核心靶点。GO功能富集分析共得到5 437个BP条目,KEGG信号通路富集分析筛选得到434条信号通路。结论:柴胡-黄芩可通过多成分、多靶点、多通路治疗CRF。

Objective: To study on the action mechanism of Chaihu(Radix Bupleuri)-Huangqin(Radix Scutellariae) in treating chronic renal failure(CRF) based on network pharmacology.Methods: The active components and related targets of Chaihu and Huangqin were retrieved based on the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).CRF related targets were retrieved through online mendelian inheritance in man(OMIM) database and GeneCards database.The online tool Draw Venn Diagram was used to take the intersection of the relevant targets of the active ingredients of Chaihu and Huangqin, and CRF related targets and draw the Wayne diagram.The intersection targets obtained are the potential targets of Chaihu-Huangqin for CRF treatment.Then the network diagram of "active ingredients potential targets" was constructed by using the software Cytoscape 3.8.0.The STRING11.0 database was used to construct a potential target protein-protein interaction(PPI) network, and to screen the core targets of Chaihu-Huangqin for CRF treatment.Then the potential targets were introduced into the Metascape platform for biological process(BP) analysis in gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) signal pathway enrichment analysis, and the "potential target signal pathway" network diagram was constructed by using the Cytoscape 3.8.0 software.Results: Based on TCMSP,13 active components of Chaihu, 32 active components of Huangqin and 216 related targets were obtained.A total of 2607 CRF related targets were obtained from GeneCards database and OMIM database.The active ingredient related targets were mapped to CRF related targets, and 137 potential targets of Chaihu-Huangqin were obtained for CRF treatment.A total of 6 core targets were obtained by PPI network analysis, and 5,437 BP entries were obtained by GO function enrichment analysis, and 434 signal pathways were obtained by KEGG signal pathway enrichment analysis and screening.Conclusion: Chaihu-Huangqin can treat CRF through multiple components, multiple targets and multiple pathways.