基于数据挖掘和网络药理学探讨含党参方剂治疗慢性咽炎用药规律及分子机制

A study on the regularity and molecular mechanism of treating chronic pharyngitis with the Dangshen containing prescription based on data mining and network pharmacology

目的:探讨党参治疗慢性咽炎的用药规律及其作用机制,为党参的临床应用及中药资源的开发提供参考。方法:基于数据挖掘的方法,运用SPSS Modeler和Python 3.7软件对治疗慢性咽炎且含有党参的方剂从性味归经、常用药物配伍及组方规律等方面进行分析,在此基础上,利用网络药理学方法分析党参治疗慢性咽炎的分子机制,并运用Cytoscape软件进行可视化处理,运用AutoDock、PyMOL等软件进行分子对接,最后用计算机分子模拟的方法验证“蛋白-配体”复合物的稳定性。结果:共得到125首治疗慢性咽炎的含党参方剂,发现21味高频药物,关联规则得到40个高频药物组合,聚类分析得到4组药物聚类组合,因子分析共提取到11个公因子。网络药理学筛选得到党参的化学成分31个,38个药物疾病交集基因,京都基因与基因组百科全书(KEGG)富集分析得到65条通路。分子对接结果显示半胱氨酸蛋白酶3(Caspase 3,CASP3)与豆甾醇的结合活性最强。结论:党参通过调节表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、CASP3、周期蛋白D1(Cyclin D1,CCND1)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)等靶点,干预EB病毒感染、缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、磷脂酰肌醇3激酶(Phosphatidylinositol3-kinase,PI3K)-蛋白激酶B(Akt)等信号通路发挥对慢性咽炎的治疗作用,为后续研究及党参的资源利用提供了依据。

Objective:To explore the regularity and molecular mechanism of the Dangshen(Radix Codonopsis)containing prescription in treating chronic pharyngitis,and to provide reference for the clinical application and new drug research development of Dangshen.Methods:Based on the method of data mining,SPSS Modeler and Python 3.7 software were used to analyze the flavor and meridian tropism,common drug compatibility and prescription rules of the prescription containing Dangshen in theO treatment of chronic pharyngitis.Then,network pharmacology method was used to analyze the molecular mechanism of Dangshen in the treatment of chronic pharyngitis,and Cytoscape software was used for visualization.In this study,software such as AutoDock and PyMOL were used for molecular docking.Finally,the stability of the protein-ligand complex was verified by computer molecular simulation.Results:A total of 125 prescriptions containing Dangshen were obtained for treating chronic pharyngitis,and 21 high-frequency drugs were found.Forty high-frequency drug combinations were obtained by association rules,four groups of drug cluster combinations were obtained by cluster analysis,and 11 common factors were extracted by factor analysis.A total of 31 chemical components and 38 drug-disease intersection genes were screened by network pharmacology,and 65 pathways were obtained by KEGG enrichment analysis.Molecular docking results showed that CASP3 had the strongest binding activity with stigmasterol.Conclusion:Dangshen plays a therapeutic part in diabetes through the regulation of core targets,such as EGFR,CASP3,CCND1,VEGFA and through intervention in Epstein-Barr virus infection,HIF-1 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and other signaling pathways,which provide a basis for further study and the resource utilization of Dangshen.