基于网络药理学探究麻黄附子细辛汤治疗哮喘的分子作用机制

Molecular mechanism of Mahuang Fuzi Xixin Decoction in the treatment of asthma based on network pharmacology

目的基于网络药理学方法探究麻黄附子细辛汤治疗哮喘的关键活性成分及分子机制。方法在中药系统药理学数据库与分析平台,检索并筛选麻黄附子细辛汤活性成分及药物靶点,并用Uniprot数据库进行靶点标准化处理。利用毒性与基因比较数据库检索并获取哮喘的相关基因。通过维恩图将药物靶点与疾病靶点取交集得到治疗靶点。将治疗靶点导入STRING数据库进行分析,构建蛋白质-蛋白质相互作用网络。以度值、中介中心性、接近中心性三者平均值以上的靶点作为关键治疗靶点。最后对关键靶点进行GO功能富集分析和KEGG信号通路分析。结果通过查阅文献及分析,结果显示麻黄附子细辛汤的5个主要活性成分为槲皮素、木犀草素、山柰酚、β-谷甾醇、柚皮素。关键靶点涵盖肿瘤坏死因子(TNF)、白细胞介素-6、TP53等30个靶点,KEGG富集分析得出麻黄附子细辛汤涉及TNF信号通路、Toll样受体信号通路等15个主要信号通路。GO富集显示麻黄附子细辛汤治疗哮喘的生物过程有124个、分子功能24个、细胞组成12个。结论麻黄附子细辛汤治疗哮喘可能存在多通路、多靶点、多成分的共同作用,为哮喘的治疗提供了生物信息学基础。

Objective To explore the key active components and molecular mechanism of Mahuang Fuzi Xixin Decoction in the treatment of asthma based on network pharmacology.Methods The active components and drug targets of Mahuang Fuzi Xixin Decoction were searched and screened in traditional Chinese medicine systems pharmacology database and analysis platform,and the target was standardized by Uniprot database.The genes related to asthma were retrieved by using comparative toxicogenomics database.The therapeutic target was obtained by intersection of drug target and disease target by Venn diagram.The therapeutic targets were imported into the STRING database for analysis,and the proteinprotein interaction network was constructed.The target greater than the average value of degree,betweenness centrality,and closeness centrality was the key target.Finally,GO enrichment analysis and KEGG signaling pathway analysis were carried out for the key targets.Results The results of literature review and analysis showed that there were five main active ingredients in Mahuang Fuzi Xixin Decoction:quercetin,luteolin,kaempferol,β-sitosterol,and naringenin.The key targets include tumor necrosis factor(TNF),interleukin-6,TP53,etc.KEGG enrichment analysis showed that Mahuang Fuzi Xixin Decoction involved 15 major signaling pathways including TNF signaling pathway and Toll-like receptor signaling pathway.GO enrichment showed that there were 124 biological processes,24 molecular functions,and 12 cell compositions in the treatment of asthma by Mahuang Fuzi Xixin Decoction.Conclusion Mahuang Fuzi Xixin Decoction in the treatment of asthma may have multi-channel,multi-target,multi-component joint effect,the treatment of asthma provides the basis of bioinformatics.