基于网络药理学和分子对接探讨艾迪注射液治疗结直肠癌作用机制研究

Study on the mechanism of action of Aidi injection in the treatment of colorectal cancer based on network pharmacology and molecular docking

目的运用网络药理学及分子对接技术探讨艾迪注射液治疗结直肠癌(CRC)的有效活性成分及潜在作用机制。方法从TCMSP、TCM-ID数据库及文献检索中提取艾迪注射液的主要活性物质,并使用SwissTargetPrediction数据库进一步确定其可能的作用靶标;从GeneCards、OMIM、DisGeNET数据库中获取CRC疾病基因靶点。运用STRING数据库及Cytoscape 3.9.1制作“药物活性成分靶点”及PPI网络图。运用Metascape数据库对交集靶点进行GO和KEGG富集分析。运用分子对接验证关键成分与疾病分子间的联系。结果共筛选出39个艾迪注射液有效成分,684个疾病分子,与CRC共有169个靶点。GO功能富集结果显示有188个分子功能、108个细胞组成、1845个生物过程。KEGG分析得到200条通路途径。分子对接结果显示,艾迪注射液核心成分华良姜素、山柰酚、槲皮素等,与疾病分子TP53、BCL2、AKT1、CCND1、CASP3对接良好。结论艾迪注射液可能通过华良姜素、山柰酚、槲皮素等活性成分调节TP53、BCL2、AKT1、CCND1、CASP3等核心靶点从而治疗CRC。

Objective To explore the active ingredients and potential mechanism of action of Aidi injection in the treatment of colorectal cancer(CRC)using network pharmacology and molecular docking technology.Methods The main active substances of Aidi injection were extracted from TCMSP,TCM-ID databases and literature search,and its possible targets of action were further identified using SwissTargetPrediction database.Gene targets of CRC disease were obtained from GeneCards,OMIM,and DisGeNET databases.STRING database and Cytoscape 3.9.1 were used to make“active ingredient-target”and PPI network diagram.GO and KEGG enrichment analyses of the intersected targets were performed using Metascape database.Molecular docking was used to verify the linkage between key components and disease molecules.Results A total of 39 active ingredients of Aidi injection were screened,and 684 disease molecules were screened,with a total of 169 common targets with CRC.The results of GO functional enrichment showed 188 molecular functions,108 cellular components,and 1845 biological processes.KEGG enrichment analyses showed 200 pathways.The molecular docking results showed that the core components of Aidi injection,such as jaranol,kaempferol and quercetin,docked well with disease molecules TP53,BCL2,AKT1,CCND1 and CASP3.Conclusion Aidi injection may regulate core targets such as TP53,BCL2,AKT1,CCND1 and CASP3 through active ingredients such as jaranol,kaempferol and quercetin to treat CRC.