基于网络药理学探讨“黄芪-当归-大枣”角药补气养血的分子机制

Study on the Molecular Mechanism of “Astragalus-Angelica-Jujube” Triangular Drugson Tonifying Qi and Nourishing Blood Based on Network Pharmacology

目的运用网络药理学探讨"黄芪-当归-大枣"角药补气养血的分子机制。方法利用中药系Cytoscape软件构建蛋白互作PPI网络,获得关键靶点。借助DAVID数据库对筛选靶点进行GO功能和KEGG通路富集分析。进一步构建气血两虚小鼠模型,灌胃"黄芪-当归-大枣"水煎剂,检测各组PTGS2 mRNA表达水平与肿瘤坏死因子-α(TNF-α)含量,完成验证实验。结果筛选得到"黄芪-当归-大枣"角药化学成分47个,预测作用靶点43个,关键靶点10个,生物功能主要定位在内质网膜和线粒体,通过介导癌症大枣"角药可调控气血两虚小鼠中PTGS2 mRNA表达,降低TNF-α释放,进而抑制TNF信号通路的激活,进一步证实了预测的可靠性。结论本研究深入诠释"黄芪-当归-大枣"角药补气养血作用多成分、多靶点和多通路的复杂机制,为其进一步临床应用和功能食品开发提供科学依据。

Objective Using network pharmacologyto explore the molecular mechanism of"Astragalus-Angelica-Jujube"triangular drugs on tonifying Qi and nourishing blood.Methods The active ingredients and putative targets of Astragalus,Angelica,Jujube were collected from the Traditional Chinese Medicine System Pharmacology(TCMSP)platform.Protein interaction(PPI)network was constructed by STRING database and Cytoscape software to obtain key targets.The analysis of GO function and KEGG pathways were carried out from DAVID database.The model of Qi-blood deficiency in mice was then established,and the water decoction of"Astragalus-Angelica-Jujube"was given by gavage.The PTGS2 mRNA expression level and TNF-αcontents in each group were measured,the validation experiment was completed.Results Totally,the 47 chemical components of"Astragalus-Angelica-Jujube"were collected,with 43 predicted targets and 10 key targets.The biological function of"Astragalus-Angelica-Jujube"triangular drugs was mainly located in the endoplasmic reticulum membrane and mitochondria through cancer signaling pathways,TNF,P53,Foxo,HIF-1 signaling pathways and calcium signaling pathways which play important roles in Qi and nourishing blood.Animal experiments showed that"Astragalus-Angelica-Jujube"horn could regulate the expression of PTGS2 mRNA in mice with Qi-blood deficiency and reduce the release of TNF-α,and then,further inhibit the activation of TNF signaling pathway,which validated the reliability of the prediction.Conclusion This study provides in-depth analysis for"Astragalus-Angelica-Jujube"triangular drugs on tonifying Qi and nourishing blood with functions from multicomponent,multi-target,and multi-pathways,which provide the scientific basis for its clinical application and functional food development.