基于网络药理学的杏贝止咳颗粒治疗哮喘作用机制研究

Studies on mechanism of Xingbei Zhike Granule in treating asthma based on network pharmacology

目的通过网络药理学技术研究杏贝止咳颗粒(Xingbei Zhike Granule,XBZK)治疗哮喘的活性成分及潜在靶点,并探讨其可能的作用机制。方法通过TCMSP数据库筛选XBZK的潜在活性成分;利用Swiss Target Prediction数据库收集潜在活性成分的作用靶点,GeneCards和TTD数据库获取哮喘相关靶点;利用Cytoscape 3.7.2软件构建“中药-活性成分-作用靶点”的网络;采用String数据平台构建PPI网络并使用Cytoscape 3.7.2软件对其进行拓扑学分析;进一步利用DAVID数据库对筛选得到的靶点进行GO和KEGG通路富集分析。结果通过TCMSP数据库筛选得到199个潜在活性成分;预测138个作用靶点;筛选出哮喘相关靶点6041个;取交集得到XBZK治疗哮喘的作用靶点89个;活性成分28个,其中以柚皮素、山柰酚、木犀草素、槲皮素、鞣花酸、黄芩素为主;GO富集到基因功能222个,KEGG富集到基因通路40条,结果表明,XBZK主要通过调节PI3K-Akt信号通路、病灶黏连、Ras信号通路、FoxO信号通路以及趋化因子信号通路等来发挥治疗哮喘的作用。结论本研究首次预测了XBZK“多成分,多靶点,多通路”治疗哮喘的作用机制,为XBZK药效物质基础研究提供了理论依据。

Objective To study the active components,potential targets,and possible mechanism of Xingbei Zhike Granule(XBZK)in treating asthma by network pharmacology technology.Methods Potential active ingredients in XBZK were screened by TCMSP database.The Swiss Target Prediction database was used to collect the targets of potential active ingredients,and GeneCards and TTD databases were used to obtain asthma-related targets.The“single medicine-active components-targets”network was constructed by the software of Cytoscape 3.7.2.The PPI network was constructed by String data platform and the topological analysis was performed by Cytoscape 3.7.2.Furthermore,DAVID database was used to enrich and analyze the gene oncology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of the selected targets.Results 199 potential active ingredients were obtained by screening TCMSP database.A total of 138 targets of potential active ingredients and 6041 targets related to asthma were screened out,and 89 targets of XBZK for treating asthma were obtained by intersecting.In addition,28 active ingredients were identified,mainly including naringenin,kaempferol,luteolin,quercetin,ellagic acid and baicalein.Finally,222 GO terms of XBZK on asthma and 40 pathways were identified by GO and KEGG analysis.The results showed that XBZK mainly played a role in treating asthma by regulating PI3 K-Akt signaling pathway,focal adhesion,Ras signaling pathway,FoxO signaling pathway and chemokine signaling pathway.Conclusion The study predicts for the first time that the mechanism of XBZK may be“multi-component,multi-target,multi-pathway”in treating asthma,which provides theoretical basis for the basic researches of XBZK pharmacodynamic substances.