基于网络药理学—分子对接探讨枳术丸“异病同治”功能性消化不良和慢传输型便秘的作用机制

Exploration of the Mechanism of Functional Dyspepsia and Slow Transit Constipation of Zhizhu Pill Based on Network Pharmacology and Molecular Docking

目的基于网络药理学-分子对接方法探讨枳术丸“异病同治”功能性消化不良(FD)和慢传输型便秘(STC)的作用靶点及作用机制。方法通过TCMSP、Swiss Target Prediction等数据库筛选出枳术丸的化学成分及其作用靶点,结合GeneCards、OMIM、Drugbank、TTD、DisGeNET等数据库获取疾病靶点,采用Cytoscape 3.6.1软件绘制枳术丸“疾病-化合物-靶点”网络,借助STRING数据库及Cytoscape 3.6.1软件构建PPI网络,采用Metascape平台对枳术丸治疗FD和STC的共有靶点进行GO分析、KEGG通路分析,最后,运用AutoDock 4.2.6和PyMOL 2.4软件进行分子对接。结果筛选得到枳术丸化学成分29个、作用靶点159个,以及10个药物成分和疾病共同靶点,包括IL-6、TP53、AKT1、IL-10、TNF等5个核心靶点。GO功能分析表明,枳术丸“异病同治”涉及生物过程536个、细胞成分5个、分子功能13个。KEGG通路分析获得枳术丸“异病同治”118条信号通路。分子对接结果显示,关键成分与对应靶点具有较好的结合活性。结论枳术丸“异病同治”FD和STC可能涉及以IL-6、IL-10、TNF、AKT1等核心靶点,其作用机制可能与调控JAK-STAT信号通路、MAPK信号通路相关。

Objective:To study the action target and mechanism of homotherapy for heteropathy of Zhizhu Pill in the treatment of functional dyspepsia(FD)and slow transit constipation(STC)based on network pharmacology and molecular docking.Methods:The chemical constituents of Zhizhu Pill and its action targets were screened out through TCMSP and Swiss Target Prediction databases,and disease targets were obtained by combining GeneCards,OMIM,Drugbank,TTD and DisGeNET databases.A network of Disease-Compound-Target of Zhizhu Pill was drawn by Cytoscape 3.6.1 software,and the PPI network was constructed by STRING database and Cytoscape 3.6.1 software.The GO and KEGG pathway ananlysis of common targets of FD and STC treated by Zhizhu Pill were made by Metascape platform.Finally,molecular docking was performed by AutoDock 4.2.6 and PyMOL 2.4 software.Results:29 chemical components and 159 targets of Zhizhu Pill were selected,and 10 common targets of drug components and diseases were identified,including 5 core targets such as IL-6,TP53,AKT1,IL-10 and TNF.The GO function analysis showed that the homotherapy for heteropathy of Zhizhu Pill involved 536 biological processes,5 cell components and 13 molecular functions.The KEGG pathway analysis obtained 118 signal pathways of homotherapy for heteropathy of Zhizhu Pill.The results of molecular docking showed that the key components had good binding activity with corresponding targets.Conclusion:The core targets of FD and STC in the homotherapy for heteropathy of Zhizhu Pill may be involved the core target of IL-6,IL-10,TNF,AKT1,etc.The mechanism of action may be related to the regulation of JAK-STAT signaling pathway and MAPK signaling pathway.