基于网络药理学的中药组方“芩部丹”治疗肺结核作用机制研究

Mechanism of traditional Chinese medicine“Qinbudan”in the treatment of pulmonary tuberculosis based on network pharmacology

目的:运用网络药理学方法探索中药组方“芩部丹”治疗肺结核的作用机制。方法:运用中药系统药理学数据库与分析平台(TCMSP)检索黄芩、百部及丹参的药物活性成分及潜在靶点。结合GeneCards、OMIM、TTD及DrugBank数据库搜索肺结核的相关基因靶点。基于Uniprot数据平台对靶点的基因名称进行整理与规范,在STRING 11.0数据平台上生成“芩部丹”治疗肺结核的靶点蛋白互作网络,利用DAVID 6.8平台对靶点进行功能富集与通路分析,利用Cytoscape 3.7.1软件对“芩部丹”治疗肺结核的成分、作用靶点、信号通路进行分析与网络构建。结果:最终筛选到的“芩部丹”有效化学成分共计116个,作用靶点含有199个。“芩部丹”治疗肺结核的核心活性成分有木犀草素、汉黄芩素、黄芩素、刺槐素、刺芒柄花素、β-谷甾醇、7-甲氧基-3-甲基-2,5-二羟基-9,10-二氢菲,涉及到潜在靶点82个,关键的作用靶点有TP53、IL6、AKT1、VEGFA、EGFR、PTGS2、JUN、CASP3、STAT3、TNF。GO功能富集分析得到生物学过程373条,分子功能66条,细胞组分39条;KEGG通路富集分析获得108条信号通路,关系最密切的为TNF信号通路和细胞凋亡(P值均<0.001),其余包括T细胞受体信号通路、PI3K-Akt信号通路及结核病(P值均<0.001)。结论:基于网络药理学解释了中药组方“芩部丹”多成分、多靶点、多通路的肺结核治疗机制,为后期的临床与基础研究提供了一定的理论支持。

Objective:To explore the mechanism of“Qinbudan”in the treatment of pulmonary tuberculosis using the network pharmacology method.Methods:The effective components and potential targets of Radix Scutellariae,Radix Stemonae radix and Radix salvia were retrieved through TCMSP database.GeneCards,OMIM,TTD,and DrugBank databases were used to obtain targets of pulmonary tuberculosis.The gene name of those targets was standardized based on Unipront,and the protein interaction network of“Qinbudan”in treating pulmonary tuberculosis was generated based on STRING 11.0.The DAVID 6.8 platform was used for functional enrichment and pathway analysis.Cytoscape 3.7.1 software was used to analyze and construct the network of components,targets and pathways of“Qinbudan”in treating pulmonary tuberculosis.Results:Finally,116 effective chemical components and 199 targets of“Qinbudan”were screened out.The core effective components of“Qinbudan”in treating pulmonary tuberculosis included luteolin,wogonin,baicalein,acacetin,formononetin,β-sitosterol and 7-methoxy-3-methyl-2,5-dihydroxy-9,10-dihydrophenanthrene.And 82 potential targets were involved,and the key targets were TP53,IL6,AKT1,VEGFA,EGFR,PTGS2,JUNP3,STAT3,TNF.A total of 373 biological process terms,66 molecular function terms and 39 cell composition terms were found by GO enrichment analysis;108 pathways were found by KEGG pathway analysis,TNF signaling pathway(P<0.001)and apoptosis(P<0.001)were the major pathways,T cell receptor signaling pathway(P<0.001),PI3K-Akt signaling pathway(P<0.001)and tuberculosis(P<0.001)were also included.Conclusion:Multi-component,multi-target and multi-pathway of the mechanism of“Qinbudan”in treating pulmonary tuberculosis were explored based on network pharmacology,which provided some theoretical support for later clinical and basic researches.