基于网络药理学和分子对接探究五指毛桃治疗重症肌无力的作用机制

Study on the Pharmacological Mechanism of Fici HirtaeRadix in Treating Myasthenia Gravis based on NetworkPharmacology and Molecular Docking

目的:利用网络药理学和分子对接技术预测五指毛桃治疗重症肌无力(Myasthenia Gravis,MG)的活性成分和靶点,并探讨其潜在的作用机制。方法:通过中药系统药理学数据库平台(TCMSP)、SwissADME、OMIM、GeneCards等数据库获取五指毛桃作用靶点及MG的疾病靶点间的交集靶点,利用STRING数据库平台解析各靶点间的相互作用、构建PPI网络图。利用Cytoscape 3.9.0软件进行“活性成分-疾病靶点”网络分析,在此基础上采用David数据库进行GO与KEGG基因功能富集分析。筛选出五指毛桃关键活性成分和靶基因后,利用Autodock vina和PyMol软件将活性成分与重要靶点进行分子对接,验证结合活性。结果:从五指毛桃中筛选出具有作用靶点的8个有效活性成分,预测得到TNF、IL6、EGFR、IL1B等8个五指毛桃治疗重症肌无力的可能蛋白靶点,通过介导TNF、Toll样细胞受体、PI3K-Akt、MAPK等信号通路,产生抗炎、提高自身免疫能力的作用,从而达到对抗重症肌无力的发生及进展,且初步验证得到成分与靶点间活性皆较为良好。结论:通过网络药理学和分子对接技术揭示了五指毛桃在治疗重症肌无力时多成分、多靶点、多通路的作用特点,并挖掘出五指毛桃治疗重症肌无力的可能靶点及信号转导机制。

Objective:To predict the active components and targets of Fici Hirtae Radix in the treatment of Myasthenia Gravis(MG)using network pharmacology and molecular docking technology,and to explore its potential mechanism.Methods:The intersection targets between the action targets of Fici Hirtae Radix and the disease targets of MG were obtained through TCMSP,SwissADME,OMIM,GeneCards and other databases,and the interactions between the targets were resolved and PPI network diagrams were constructed using the STRING database platform.Active ingredient-disease target network analysis was conducted using Cytoscape 3.9.0 software,based on which functional enrichment analysis of GO and KEGG genes was performed using David's database.After screening the key active ingredients and target genes,the active ingredients were molecularly docked to the important targets using Autodock vina and PyMol software to verify the binding activity.Results:Eight effective active components with targets were screened from Fici Hirtae Radix,and eight possible protein targets of TNF,IL6,EGFR and IL1 B in the treatment of MG were predicted.By mediating TNF,Toll-like cell receptor,PI3K-Akt,MAPK and other signaling pathways,anti-inflammatory and improving their immune ability were produced,so as to achieve the occurrence and progress of myasthenia gravis,and the activity between components and targets was preliminarily verified.Conclusion:The characteristics of multi-component,multi-target and multi-pathway in the treatment of MG were revealed by network pharmacology and molecular docking technology,and the possible targets and signal transduction mechanisms of Fici Hirtae Radix in the treatment of myasthenia gravis were explored.