基于网络药理学与分子对接技术探讨小儿清热止咳口服液治疗小儿发热作用机制  

Mechanism of Xiao’er Qingre Zhike Koufuye in Treatment of Fever in Children Based on Network Pharmacology and Molecular Docking Technology

作　　者：武薇 徐梓轩 赵文宇 李姿柔 崔晓燕 张素平 于永洲 WU Wei;XU Zi-xuan;ZHAO Wen-yu;LI Zi-rou;CUI Xiao-yan;ZHANG Su-ping;YU Yong-zhou(Chengde Medical University,Chengde,067000,China;Hebei Institute for Drug and Medical Device Control,Shijiazhuang,050000,China;Hebei Key Laboratory of Nerve Injury and Repair,Chengde,067000,China)

机构地区：[1]承德医学院,承德067000 [2]河北省药品医疗器械检验研究院,石家庄050000 [3]河北省神经损伤与修复重点实验室,承德067000

出　　处：《神经药理学报》2022年第4期10-22,40,共14页Acta Neuropharmacologica

基　　金：河北省神经损伤与修复重点实验室开放课题项目(No.NJKF202103);河北省省级科技计划资助项目(No.216Z2501G,No.H2022406026,No.H2022329001);承德医学院高层次人才科研启动基金项目(No.202106);2022年河北省大学生创新创业训练计划项目(No.S202210093029,No.2022112)。

摘　　要：目的:通过构建小儿清热止咳口服液成分与靶点和蛋白相互作用网络,进行富集分析并确定涉及的生物过程和通路,从而研究小儿清热止咳口服液治疗小儿发热的潜在作用机制。方法:通过检索TCMSP数据库筛选出小儿清热止咳口服液的活性成分,预测其靶点,并与Genecards数据库以及DrugBank数据库获得的发热相关靶点取交集,进而得到小儿清热止咳口服液治疗发热的潜在作用靶点。将对比结果处理后输入Cytoscape 3.7.2软件中构建“小儿清热止咳口服液成分-化合物-发热靶点”网络,利用String数据库和Cytoscape 3.7.2构建蛋白相互作用网并得到关键靶点。通过DAVID v6.8数据库进行GO生物功能和KEGG通路富集分析,并借助Cytoscape 3.7.2将富集结果可视化。最后将关键化合物与关键靶点进行分子对接。结果:分析结果得到小儿清热止咳口服液160个活性成分,活性成分靶点为584个,4137个已知的小儿发热相关的靶点基因。取疾病基因与药物靶点的交集得到346个交集靶点,经蛋白相互作用网络及拓扑分析后得到18个核心靶点。富集分析显示主要通路集中在神经活性配体-受体相关通路、免疫炎症通路,也有神经毒素成瘾、病毒感染等其他通路富集其中。进一步筛选核心靶点及化合物进行分子对接结果显示Casp3、CREB1、Fos、IL-1B、IL-6、INS、Jun以及MYC作为核心靶点蛋白可与D-去甲伪麻黄碱(D-norpseudoephedrine)、β-谷甾醇(Beta-sitosterol)、苦参碱(Matrine)以及麻黄碱(Ephedrine)等小分子稳定结合。结论:该研究通过网络药理学及分子对接的方法,获得小儿清热止咳口服液中的可能活性成分及小儿发热潜在作用靶点,并预测了小儿清热止咳口服液治疗小儿发热的代谢、信号通路传导等多种途径,从而达到治疗小儿发热的目的,为小儿清热止咳口服液治疗小儿发热的作用机制提供了理论依据,为进一步研究相�Objective:By constructing the interaction networks between the compositions of Xiao’er Qingre Zhike Koufuye and target networks and proteins,we conducted the enrichment analysis to determine the biological processes and involved pathways,we also studied the potential action mechanism of fever in children.Methods:The active components of Xiao’er Qingre Zhike Koufuye were selected and the target points were predicted by searching TCMSP database,and the potential action targets were obtained by crossing Genecards database with Drug Bank database of the fever-related targets.After processing the comparison results,the targets were input into Cytoscape3.7.2 software to build the“Xiao’er Qingre Zhike Koufuye ingredientscompounds-fever targets”network,and the String database and Cytoscape3.7.2 database were used to construct the protein interaction network and to obtain the key targets.The GO biofunction and KEGG pathway enrichment analysis were later performed through the DAVID v6.8 database and the enrichment results were visualized with Cytoscape3.7.2.Finally,the molecular docking of the key compounds and the targets were performed.Results:160 active components,584 active component targets,and 4137 known fever in children-related target genes were obtained.The interaction of disease genes and drug targets yielded 346 intersection targets,and 18 core targets were obtained by the protein interaction network and topological analysis.Enrichment analysis showed that the main pathways focused on neuroactive ligand-receptor-related pathways,immune inflammation pathways,and other pathways such as neurotoxin addiction and viral infection.Further screening of core targets and compounds for molecular docking showed that Casp3,CREB1,Fos,IL-1B,IL-6,INS,Jun,and MYC as core target proteins could stably bind to small molecules such as D-norpseudoephedrine,beta-sitosterol,matrine and ephedrine.Conclusion:Through network pharmacology and molecular docking,our study found the possible active ingredients of Xiao’er Qingre Zh

关 键 词：小儿清热止咳口服液 小儿发热 网络药理学 分子对接 

分 类 号：R917[医药卫生—药物分析学]