基于网络药理学与分子对接技术的鲜竹沥治疗“咳、喘、痰”机制及其质量标志物预测分析

Predictive analysis of mechanism and quality marker of fresh bamboo sap on“cough,asthma,sputum”based on network pharmacology and molecular docking technology

目的应用网络药理学和分子对接方法,对鲜竹沥发挥“咳、喘、痰”作用的机制及潜在的质量标志物(quality marker,Q-Marker)预测分析。方法采用干馏法和火烤法制备鲜竹沥,对鲜竹沥的指纹图谱进行研究,筛选并预测其中14个成分的潜在作用靶点及通路,结合文献数据库分析确定“咳、喘、痰”病症的靶基因;取药物与疾病交集基因,将交集基因上传String数据库进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,利用Rstudio的clusterProfiler功能对交集基因进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;预测鲜竹沥的Q-Marker,并运用分子对接软件对部分关键靶点及其对应成分进行分子对接,验证网络分析结果。结果采用指纹图谱研究得到8批干馏法、火烤法的鲜竹沥主要活性成分,经网络药理学及分子对接分析鲜竹沥对“咳、喘、痰”病症的治疗作用,推测鲜竹沥的Q-Marker为香草酸、对乙基苯酚、丁香醛、二氢丁香酚、对乙烯基愈创木酚,主要通过调节炎症反应、环磷酸腺苷(cyclic adenosine monophosphate,cAMP)信号通路、缺氧诱导因子-1α(hypoxiainducible factor-1α,HIF-1α)信号通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路等重要生物通路来发挥止咳、平喘、化痰的作用。结论通过预测鲜竹沥的Q-Marker,为提升其质量控制标准奠定了基础,同时也为鲜竹沥功效关联物质的研究及作用机制的阐释提供参考,为其二次开发以及扩大临床使用范围提供参考依据。

Objective To predict and analyze the mechanism and potential quality marker(Q-Marker)of fresh bamboo sap in the treatment of“cough,asthma,sputum”based on network pharmacology and molecular docking methods.Methods Fresh bamboo sap was prepared by dry distillation and fire roasting.The fingerprint of fresh bamboo sap was studied,and the potential targets and pathways of 14 components were screened and predicted.Target genes of“cough,asthma,sputum”disease were determined by combining literature database.Intersection genes of drug and disease were taken,protein-protein interaction(PPI)analysis was performed by String database,gene ontology(GO)functions and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis on intersection genes were performed by clusterProfiler function of Rstudio.Q-Markers of fresh bamboo sap were predicted,and molecular docking software was used to perform molecular docking on key targets and its corresponding components to verify the network analysis results.Results Eight batches of main active ingredients of fresh bamboo sap which prepared by dry distillation and fire roasting were obtained by fingerprint study.The therapeutic effects of fresh bamboo sap on“cough,asthma,sputum”symptoms were analyzed by network pharmacology and molecular docking.Q-Markers were vanillic acid,p-ethylphenol,syringaldehyde,dihydroeugenol and p-vinylguaiacol,which mainly regulated inflammation,cyclic adenosine monophosphate(cAMP)signaling pathway,hypoxia-inducible factor hypoxia-inducible factor-1α(HIF-1α)signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway and other important biological pathways to play the role of relieving cough,asthma and phlegm.Conclusion By predicting the Q-Markers of fresh bamboo sap,it has laid a research foundation for improving its quality control standards,and provides a reference for study of related substances of fresh bamboo sap and explanation of mechanism.It provides a reference basis for its secondary development and the potential to expand the scope of clinical use.