目的 探讨儿童清咽解热口服液治疗上呼吸道感染的潜在机制。方法 分别从TCMSP和Swiss Target Prediction数据库中提取儿童清咽解热口服液组方药物的潜在生物活性成分和相应的靶点，疾病靶点从GeneCards数据库中获取。通过Cytoscape软件构建"中药材-化合物-靶点"网络，并通过STRING web平台分析蛋白质-蛋白质相互作用（PPI）网络。在DAVID平台上进行基因本体（GO）和京都基因与基因组百科全书（KEGG）功能富集分析，利用Maestro软件进行分子对接。采用RAW264.7细胞进行体外Western blottitng和免疫荧光实验验证。结果 共筛选儿童清咽解热口服液组方药材含有的41种有效化合物，177种成分和疾病的共同靶点。其中，黄芩苷、柴胡皂苷、槲皮素、鱼腥草素等是重要的活性化合物。PI3K、Akt、EGFR、MAPK3、GRB2、PIK3R1等是关键靶点。PI3K/Akt信号通路、HIF-1信号通路和FOXO信号通路被认为是3条重要的信号通路。相关成分、靶点和通路与抗炎、抗病毒和免疫调节有关。分子对接结果提示，筛选的12个关键靶点可与大多数主要活性化合物紧密结合。Western blotting和免疫荧光实验结果显示，儿童清咽解热口服液可以抑制PI3K和Akt的蛋白表达，与网络药理学的预测结果一致。结论 儿童清咽解热口服液主要通过调节PI3K/Akt等信号通路发挥治疗儿童急性上呼吸道感染的作用。

Objective To investigate the potential mechanism of Ertong Qingyan Jiere Oral Liquid (EQJOL) in the treatment of upper respiratory tract infection (URTI). Methods The active ingredients and their corresponding targets were extracted from the TCMSP and Swiss Target Prediction databases, respectively, and the disease targets were obtained from the GeneCards database. Then, Cytoscape software was used to construct the "Chinese medica-compound-target" network, and the protein-protein interaction(PPI) network was analyzed by STRING web platform. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis were performed on DAVID platform, and then molecular docking was performed using Maestro software. Finally, RAW264.7 cells were used for in vitro Western blotting and immunofluorescence verification. Results A total of 41 effective compounds and 177 common targets of drugs and diseases were found to be associated with URTI. Among them, baicalin, saikosaponin, quercetin and houttuynin are important active compounds. PI3K, Akt, EGFR, MAPK3, GRB2 and PIK3R1 are the key targets. PI3K/Akt signaling pathway, HIF-1 signaling pathway and FOXO signaling pathway are considered to be three important signaling pathways. Relevant components, targets and pathways are related to anti-inflammatory, antiviral and immune regulation. Molecular docking results suggested that these 12 key targets could bind tightly to most of the major active compounds. Western blotting and immunofluorescence results showed that EQJOL inhibited the expression of PI3K and Akt, which was consistent with the prediction of network pharmacology. Conclusions EQJOL has a therapeutic effect in children with acute URTI mainly by regulating the PI3K/Akt signaling pathway.

R285.5

河南省医学科技攻关计划项目（LHGJ20210283）