基于网络药理学和分子对接探讨中药何首乌改善阿尔茨海默病的作用机制

Action mechanism of radix polygoni multiflori in the improvement of Alzheimer′s disease based on network pharmacology and molecular docking

目的基于网络药理学结合分子对接方法探讨中药何首乌改善阿尔茨海默病(AD)的有效成分及作用机制。方法利用文献检索获取何首乌活性成分,运用SwissADME和SwissTargetPrediction数据库对其相关靶点进行筛选、预测,并通过GeneCards、DisGeNET及OMIM数据库搜集AD疾病相关靶点;利用STRING数据库、Cytoscape3.7.1软件构建药物-疾病交集靶点蛋白互作网络;通过Metascape数据库进行GO生物功能和KEGG通路富集分析;运用Cytoscape3.7.1软件构建“成分-靶点-通路”网络,分析获取网络中的关键靶点和对应成分,并利用分子对接进行初步验证。结果文献检索收集到何首乌化学成分131个,经筛选后得到何首乌改善AD潜在活性成分36个,预测得到靶点494个,改善AD潜在作用靶点206个,核心靶点8个;GO生物功能富集分析涉及生物过程2471个、细胞组分165个、分子功能270个,KEGG通路富集分析得339条通路,主要作用于表皮生长因子受体(EGFR)信号通路、AD、5-羟色胺能突触通路等;通过分子对接发现何首乌主要活性成分与核心靶蛋白结合并展现出较好的亲和力。结论中药何首乌改善AD的作用机制主要是通过保护神经、抑制炎症、延缓衰老等途径发挥作用,可为中药何首乌改善AD的进一步研究提供科学依据。

Objective To explore the key compounds and action mechanism of radix polygoni multiflori in the improvement of Alzheimer′s disease(AD)based on the combination of network pharmacology and molecular docking.Methods The active components of radix polygoni multiflori were obtained by literature search,SwissADME and SwissTargetPredition databases were used to screen and predict the relevant targets.AD-related targets were collected from GeneCards,DisGeNET and OMIM databases.The drug-disease intersection target protein interaction network was constructed using STRING database and Cytoscape3.7.1 software.Metascape databases was used for GO biological function and KEGG pathway enrichment analysis.The network of"compound-target-pathway"was constructed through Cytoscape3.7.1 software to analyze and obtain the key targets and their corresponding compounds in the network,and their results were verified by the molecular docking.Results A total of 131 chemical compounds of radix polygoni multiflori were obtained by literature mining.After screening,36 potential active ingredients of radix polygoni multiflori for improving AD were obtained,494 targets were predicted,206 potential AD action targets were improved,and 8 key targets were obtained.The enrichment analysis of GO biological function involved 2471 biological processes,165 cell compounds,270 molecular functions,339 signal pathways were obtained from KEGG pathway enrichment,which mainly acted on epidermal growth factor receptor(EGFR)signal pathway,AD,serotonergic synapse pathway and so on.Molecular docking analysis showed the main active components of radix polygoni multiflori were bound to key target proteins and showed good affinity.Conclusions The action mechanism of radix polygoni multiflori in the improvement of AD is mainly through the protection of nerve,inhibition of inflammation,delaying aging and other ways,and provide a scientific basis for the further study of radix polygoni multiflori in the improvement of AD.