基于网络药理学和分子对接探讨淫羊藿抗肿瘤作用机制

Study on antitumor mechanism of Epimedium based on network pharmacology and molecular docking

目的通过网络药理学和分子对接方法探讨淫羊藿抗肿瘤的作用机制。方法利用TCMSP数据库获取淫羊藿的活性成分以及相对应的靶点,利用Genecards、OMIM数据库获取疾病靶点,绘制药物-疾病韦恩图,获得其共同靶点;利用Cytoscape 3.8.2软件构建“淫羊藿活性成分-疾病靶点”网络可视化关系图;利用STRING数据库和Cytoscape 3.8.2软件构建蛋白相互作用网络,并进行网络拓扑分析;利用R x644.0.5软件,对相关靶点进行GO和KEGG富集分析,了解淫羊藿抗肿瘤可能的生物过程及其通路;最后利用SYBYL 2.0软件分子对接进行半柔性对接反向验证。结果筛选出淫羊藿活性成分23个,靶点193个;疾病相关靶点8169个,活性成分与疾病两者共同靶点173个;蛋白互作网络显示TP53、AKT1、JUN、CASP3等靶点基因在淫羊藿抗肿瘤的生物网络中起重要作用;潜在作用靶点涉及2592条生物学功能、176条通路。分子对接结果显示淫羊藿活性化合物与多个疾病关键靶点具有较高结合能力,对接评分较高的为淫羊藿苷与CASP3靶点蛋白。结论淫羊藿抗肿瘤具有多靶点和多通路的潜在作用机制,为其进一步研究提供参考。

Objective To explore the antitumor mechanism of Epimedium by means of network pharmacology and molecular docking.Methods The active components and corresponding targets of Epimedium were obtained by TCMSP database,the disease targets were obtained by Genecards and OMIM database,and the drug disease Wayne diagram was drawn to obtain their common targets;The network visualization diagram of"Epimedium active components disease targets"was constructed by using Cytoscape 3.8.2 software;The protein-protein interaction network was constructed by using STRING database and Cytoscape 3.8.2 software,and the network topology analysis was performed;Using R x644.0.5 software,GO and KEGG enrichment analysis of relevant targets were carried out to understand the possible biological process and pathway of Epimedium antitumor;Finally,the reverse verification of semi flexible docking is carried out by using SYBYL 2.0 software.Results 23 active components and 193 targets of Epimedium were screened;8169 disease-related targets and 173 common targets of active ingredients and diseases;Protein interaction network showed that TP53,AKT1,JUN,CASP3 and other target genes played an important role in Epimedium antitumor biological network;Potential targets involve 2592 biological functions and 176 pathways.The results of molecular docking showed that the active compounds of Epimedium had high binding ability to several key disease targets,and the higher docking scores were Icariin and CASP3 target proteins.Conclusion Epimedium has the potential mechanism of multi-target and multi-channel anti-tumor,which provides a reference for its further research.