基于网络药理学和分子对接技术探讨小儿热速清口服液治疗手足口病的物质基础及作用机制

Material basis and mechanism of Xiao'er Resuqing Oral Liquid on hand,foot and mouth disease based on network pharmacology and molecular docking

通过网络药理学及分子对接技术探讨小儿热速清口服液治疗手足口病(hand,foot and mouth disease,HFMD)的物质基础及分子机制。首先通过TCMSP平台、Batman数据库结合相关文献补充筛选小儿热速清口服液中8味中药候选的化学成分。然后通过PubChem和Swiss Target Prediction数据库进行相关靶点分析,通过GeneCards平台挖掘HFMD的相关靶点,取2个靶点交集获得小儿热速清口服液治疗HFMD的潜在靶点。通过Cytoscape软件构建小儿热速清口服液治疗HFMD的"药物-成分-靶点-疾病"网络图。基于STRING平台结合Cytoscape软件构建小儿热速清口服液治疗HFMD蛋白相互作用(protein-protein interaction,PPI)网络,筛选核心靶点。利用Metascape平台进行KEGG及GO过程富集分析,并利用Autodock vina 1.1.2软件实现潜在药效成分及关键靶点分子对接。研究结果显示,共收集到小儿热速清口服液118个潜在药物成分,潜在治疗HFMD靶点123个。PPI网络表明主要涉及AKT1,MAPK1,IL6,VEGFA,EGFR,TNF,HRAS,CCND1,CXCL8等23个核心靶点。GO分析过程涉及(P<0.01)381个生物过程、127个细胞组分和117个分子功能。KEGG分析(P<0.01)共富集161条信号通路,KEGG通路注释表明主要与TNF信号通路、IL-17信号通路、TRP通道的炎症介质调节、细胞因子与细胞因子受体的相互作用等有密切关系。分子对接结果显示,主要活性成分与核心靶点均有较好的结合作用。该研究初步揭示了小儿热速清口服液可通过多成分、多靶点、多通路治疗HFMD,为进一步研究其有效成分及分子机制提供依据。

This paper aimed to investigate the active components and molecular mechanism of Xiao'er Resuqing Oral Liquid on hand,foot and mouth disease(HFMD)based on network pharmacology and molecular docking methods.The potential active components of 8 herbs in Xiao'er Resuqing Oral Liquid were selected through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),Batman database and relevant literature consultation.Then related targets for the medicine were analyzed through PubChem and Swiss Target Prediction database,while related targets for HFMD were analyzed through GeneCards platform.The common targets for medicine and disease were put into STRING database to obtain the potential targets of Xiao'er Resuqing Oral Liquid for treatment of HFMD.The Cytoscape software was used to establish the"herbs-components-targets-disease"network.The protein-protein interaction(PPI)network was constructed based on STRING platform and Cytoscape software to screen the core targets.Based on Metascape platform,GO function enrichment analysis and KEGG signal pathway enrichment analysis were carried out.The main active components and potential key targets of Xiao'er Resuqing Oral Liquid were verified by molecular docking with Autodock vina 1.1.2 software.A total of 118 potential active components and 123 potential targets for treatment of HFMD were collected.PPI network indicated a total of 23 key targets,such as AKT1,MAPK1,IL6,VEGFA,EGFR,TNF,HRAS,CCND1,and CXCL8.GO function enrichment analysis results showed that there were 381 GO biological processes,127 GO cellular components,and 117 GO molecular functions(P<0.01).KEGG enrichment analysis showed that 116 signal pathways were obtained(P<0.01),and the results showed that it was mainly associated with TNF signal pathway,IL-17 signal pathway,inflammatory mediator regulation of TRP channels,and cytokine-cytokine receptor interaction.Molecular docking results showed that the main active components all had a high binding ability with the main potential key targets.This study preliminarily investigated the multi-pathways,multi-targets and multi-components molecular mechanism of Xiao'er Resuqing Oral Liquid for treatment of HFMD,providing theoretical references for further researches on its active components and action mechanism.