分子对接技术结合网络药理学拓扑分析探讨人参-当归药对防治缺血性脑卒中的作用机制

Molecular docking technology combined with network pharmacology and topological analysis to explore the mechanism of action of the Panax ginseng-Angelica sinensis herb pair in preventing and treating ischemic stroke

目的:基于分子对接技术及网络药理学拓扑分析,探究人参-当归药对治疗缺血性脑卒中的可能机制。方法:使用中药系统药理数据库,收集人参和当归的化学成分,并在Uniprot中进行基因定位;并分析GeneCards、OMIM、TTD和DisGeNET数据库中与缺血性脑卒中相关的靶点,将其与药物作用靶点进行映射,并利用STRING和Cytoscape构建蛋白互作网络,以更好地检索关键靶蛋白;通过生物功能和通路富集分析,更深入地研究关键靶点蛋白,并使用R-studio将结果可视化。最后,借以分子对接筛选出人参-当归有效成分中与核心治疗靶点结合能力较强的化学成分。结果:发现人参-当归中含有22种化学成分,已探明靶点有110个。缺血性脑卒中相关靶点有2157个,关键靶蛋白54个。蛋白互作拓扑网络包含AKT-1、TNF等关键靶蛋白。通路富集分析发现122条相关通路,其中包括AGE-RAGE等,均与缺血性脑卒中有着密切的联系(P<0.05)。分子对接筛选到β-谷甾醇、豆甾醇等成分与AKT-1、NOS3和MAPK8有强烈结合能力。结论:人参-当归可以与AKT-1、NOS3等靶点相互作用,参与调节多种生物学反应,包括抗炎、抗氧化应激等,从而预防和治疗缺血性脑卒中。

Objective:To investigate the pharmacology-molecular docking approach of the interaction between Panax ginseng and Angelica sinensis in the treatment of ischemic stroke.Methods:The TCMSP database was used to collect all chemical components of the herbal pairing,while the Uniprot database was consulted to forecast target genes.Ischemic stroke-related targets were identified using the GeneCards,OMIM,TTD,and DisGeNET databases.AVenn diagram analysis was conducted to identify the intersection points of Panax ginseng-Angelica sinensis and ischemic stroke,then a protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape.Rstudio was employed to visualize the outcomes of GO enrichment and KEGG pathway enrichment analyses on the essential target proteins.Molecular docking was finally utilized to detect chemical components with powerful adhesion capacity.Result:Twenty-two active ingredients,110 targets related to Herb Pair Panax ginseng-Angelica sinensis,2157 targets for ischemic stroke disease were identified,with 54 intersection targets screened.PPI network mainly involved core target proteins such as AKT-1,TNF.An enrichment analysis of KEGG revealed a close association between ischemic stroke and 122 pathways(P<0.05),including AGE-RAGE.The binding capability ofβ-sitosterol and Stigmasterol to AKT-1 was demonstrated by molecular docking results.Conclusion:The potential of Panax ginseng-Angelica sinensis herb pair in treating ischemic stroke may be connected to multi-pathway AKT-1,NOS3 and MAPK8,which can act as mediators of ischemic stroke through anti-inflammation and anti-oxidative stress mechanisms.