Xu Ying-Li, Guo Shan-Shan, Cui Xiao-Lan, Shi Yu-Jing
Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2020 Dec;45(23):5745-5752. doi: 10.19540/j.cnki.cjcmm.20201022.401.
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.
本文旨在基于网络药理学和分子对接方法,研究小儿热速清口服液治疗手足口病(HFMD)的活性成分及分子机制。通过中药系统药理学数据库(TCMSP)、Batman数据库并查阅相关文献,筛选出小儿热速清口服液中8味中药的潜在活性成分。然后通过PubChem和瑞士靶点预测数据库分析该药物的相关靶点,同时通过GeneCards平台分析手足口病的相关靶点。将药物与疾病的共同靶点导入STRING数据库,获取小儿热速清口服液治疗手足口病的潜在靶点。利用Cytoscape软件构建“中药-成分-靶点-疾病”网络。基于STRING平台和Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络,筛选核心靶点。基于Metascape平台进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析。使用Autodock vina 1.1.2软件通过分子对接验证小儿热速清口服液的主要活性成分和潜在关键靶点。共收集到118个潜在活性成分和123个治疗手足口病的潜在靶点。PPI网络显示共有23个关键靶点,如AKT1、MAPK1、IL6、VEGFA、EGFR、TNF、HRAS、CCND1和CXCL8。GO功能富集分析结果显示,有381个GO生物学过程、127个GO细胞成分和117个GO分子功能(P<0.01)。KEGG富集分析显示获得116条信号通路(P<0.01),结果表明其主要与TNF信号通路、IL-17信号通路、TRP通道的炎症介质调节以及细胞因子-细胞因子受体相互作用有关。分子对接结果表明,主要活性成分与主要潜在关键靶点均具有较高的结合能力。本研究初步探讨了小儿热速清口服液治疗手足口病的多途径、多靶点、多成分分子机制,为进一步研究其活性成分和作用机制提供理论参考。