基于网络药理学及分子对接探讨加味六安煎治疗咳嗽变异性哮喘的作用机制

Mechanism of Jiawei Liu’an Decoction in the Treatment of Cough Variant Asthma Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学及分子对接技术探讨加味六安煎(JWLAD)治疗咳嗽变异性哮喘(CVA)潜在的作用机制。方法:采用中药系统药理学数据库和分析平台(TCMSP)筛选JWLAD的活性成分及其潜在靶点,利用Genecards、Drugbank、OMIM、Disgenet、TTD数据库检索CVA相关靶点。运用Cytoscape及STRING平台构建活性成分-靶点、蛋白质互作(PPI)网络,借助Metascape对共同靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析,最后由Autodock Vina实现主要活性成分及核心靶点的分子对接。结果:最终得到中药活性成分64种涉及348个潜在靶点,CVA相关靶点1290个,两者共同靶点167个。GO分析过程涉及2336条生物过程、112条细胞组分和118条分子功能。KEGG共富集169条主要涉及各种癌症通路,白细胞介素17(IL-17)信号通路、肿瘤坏死因子(TNF)信号通路、神经活性配体和受体相互作用、细胞凋亡,Toll样受体信号通路、磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路等。分子对接结果提示主要活性成分与核心靶点均有较强的亲和能力。结论:JWLAD通过多成分-多靶点-多通路综合调控网络发挥治疗CVA的作用,为后期临床和实验研究提供理论基础。

Objective:To explore the potential mechanism of Jiawei Liu’an decoction(JWLAD)in the treatment of cough variant asthma(CVA)based on network pharmacology and molecular docking technology.Methods:The active ingredients and potential targets of JWLAD were screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).CVA-related targets were searched using Genecards,Drugbank,OMIM,Disgenet and TTD databases.Cytoscape and STRING platform were used to construct an active ingredient-target,protein interaction(PPI)network,and Metascape was used to perform gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of common targets.Finally,Autodock Vina was employed to realize the molecular docking of main active ingredients and core targets.Results:Totally 64 active ingredients of JWLAJ involving 348 potential targets,1290 CVA-related targets and 167 common targets were obtained.The GO analysis process involved 2336 biological processes,112 cell components and 118 molecular functions.KEGG enriched a total of 169 items mainly related to various cancer pathways,interleukin-17(IL-17)signaling pathway,tumor necrosis factor(TNF)signaling pathway,neuroactive ligand and receptor interaction,cell apoptosis,Toll-like receptor signaling pathway and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signalling pathway,etc.The results of molecular docking suggested that the main active ingredients had strong affinity with the core targets.Conclusion:JWLAD plays a role in the treatment of CVA through a multi-component multi-target multi-pathway comprehensive regulatory network,which provides theoretical basis for future clinical and experimental research.