基于网络药理学和分子对接技术探讨小儿化积止咳方治疗咳嗽的作用机制

Mechanism of Xiaoer Huaji Zhike Prescription in the Treatment of Cough Based on Network Pharmacology and Molecular Docking

目的:本研究拟基于网络药理学和分子对接技术探讨小儿化积止咳方治疗咳嗽的作用机制。方法:通过TCMSP、Uniprot、Pubchem、SwissTargetPrediction及DisGeNET数据库获取药物的活性成分、药物靶点、疾病靶点以及药物与疾病的共同靶点。并使用Cytoscape 3.9.0软件进行蛋白互作关系(PPI)分析以及获取Hub genes,之后进行基因本体(GO)、京都基因和基因组百科全书(KEGG)分析,确定其生物学功能及调节的通路。最后进行分子对接,明确小儿化积止咳方发挥作用的主要化合物。结果:获得药物与疾病的交集靶点46个,其中10个是关键靶点,主要参与调控晚期糖基化终产物(AGE)-晚期糖基化终产物受体(RAGE)和白细胞介素17(IL-17)等信号通路。分子对接结果显示,其中4个Hub genes肿瘤坏死因子(TNF)、基质金属蛋白酶9(MMP9)、表皮生长因子受体(EGFR)、转录信号转导和激活因子3(STAT3)可以与药方中的17种化合物进行良好的结合。结论:小儿化积止咳方可能通过靶向TNF、MMP9、EGFR和STAT3等靶点,调控AGE-RAGE和IL-17等信号通路,发挥治疗咳嗽的作用。

Objective:To explore the mechanism of Xiaoer Huaji Zhike prescription in the treatment of cough.Methods:The active components,drug targets,disease targets,the common targets of drugs and diseases were obtained by TCMSP,Uniprot,Pubchem,SwissTargetPrediction,and DisGeNET databases.Cytoscape 3.9.0 software was used for protein-protein interaction(PPI)analysis to obtain Hub genes.Then,gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)analysis were performed to determine its biological function and regulation pathway.Finally,the molecular docking was carried out to clarify the main compounds of Xiaoer Huaji Zhike prescription.Results:There were 46 drug-disease intersection targets,with 10 hub genes.They were mainly involved in regulating advanced glycosylation and products(AGE)-AGE receptor(RAGE),interleukin 17(IL-17)and other signaling pathways.The results of molecular docking indicated that 4 hub genes,including tumor necrosis factor(TNF),matrix metalloproteinase 9(MMP9),epidermal growth factor receptor(EGFR)and signal transduction and activator of transcription 3(STAT3),could bind well with 17 compounds in the prescription.Conclusion:Xiaoer Huaji Zhike prescription may exert therapeutic effects on cough by targeting TNF,MMP9,EGFR and STAT3,regulating signaling pathways such as AGE-RAGE and IL-17.