结合网络药理学和分子对接探讨小儿消积止咳口服液治疗支原体肺炎的物质基础和潜在机制

Identification of bioactive compounds and potential mechanisms of Xiaoer Xiaoji Zhike Oral Liquid in treating mycoplasma pneumonia by network pharmacology and molecular docking

目的用网络药理学和分子对接的分析方法,探讨小儿消积止咳口服液治疗小儿支原体肺炎的功效网络与作用机制。方法通过化学成分分析文献,获取小儿消积止咳口服液的主要有效成分,通过SwissTargetPrediction数据库预测活性成分的潜在靶点。支原体肺炎相关靶点来自GeneCards和Disgenet数据库。筛选出疾病和成分的交集靶点,通过STRING和Cytoscape软件分析了共享靶点之间的蛋白质相互作用关系。利用DAVID数据库进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)功能富集分析。通过分子对接技术,评估活性成分与核心靶点的结合活性。结果共筛选得到小儿消积止咳口服液活性成分101个和813个成分的靶点,与306个支原体肺炎相关的靶点取交集,得到67个靶点。GO富集分析显示,相关靶点参与细胞凋亡、炎症、外来刺激等生物学过程发挥作用。KEGG富集分析显示,小儿消积止咳口服液治疗支原体肺炎的机制可能与肿瘤坏死因子(TNF)、磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、乙型肝炎、细胞凋亡等信号通路有关。通过蛋白质相互作用(PPI)网络筛选出8个核心靶点,其中,小儿消积止咳口服液活性成分对TNF、环加氧酶2(PTGS2)、甘油醛-3-磷酸脱氢酶(GAPDH)的结合能力最强。结论小儿消积止咳口服液治疗支原体肺炎具有多成分、多靶点、多通路的特点,其作用机制复杂,可能主要通过抑制炎症反应发挥作用。

Objective The efficacy network and mechanism of Xiaoer Xiaoji Zhike oral liquid in treating children with mycoplasma pneumonia were studied by network pharmacology and molecular docking analysis.Methods The main active components of Xiaoer Xiaoji Zhike oral liquid were obtained through chemical compo-sition analysis of literature.Potential targets of the above active ingredients were predicted by SwissTargetPredic-tion database.Mycoplasma pneumonia-related targets were obtained from GeneCards and Disgenet databases.The protein-protein interaction(PPI)among the intersection targets of diseases and components were analyzed by STRING and Cytoscape software.The Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)functional enrichment analysis were performed using the DAVID database.Molecular docking technique was used to evaluate the binding activity of active ingredients and core targets.Results A total of 101 active compo-nents and 813 related targets of Xiaoer Xiaoji Zhike oral liquid were selected.And 67 targets were obtained by intersecting with drug targets and 306 targets related to mycoplasma pneumonia.GO enrichment analyses showed that related targets played a role in apoptosis,inflammation,stimulation,and other biological processes.The mech-anisms of Xiaoer Xiaoji Zhike oral liquid in treating mycoplasma pneumonia may be related to tumor necrosis fac-tor(TNF),phosphatidylinotidine-3-kinase-protein kinase B(PI3K-Akt),hepatitis B,cell apoptosis and some other signaling pathways according to the results of KEGG enrichment.Eight core targets were selected through PPI network.The active ingredients of Xiaoer Xiaoji Zhike oral liquid had the strongest binding ability to TNF,prostaglandin endoperoxide synthase 2(PTGS2)and glyceraldehyde-3-phosphate dehydrogenase(GAPDH).Conclusion Xiaoer Xiaoji Zhike oral liquid for children in the treatment of mycoplasma pneumonia has the char-acteristics of multi-component,multi-target and multi-pathway,and its mechanism of action is complex,which may mainly play its role by inhibiting inflammation.