基于网络药理学探讨人参治疗阿尔茨海默病的作用

Study on the Effect of Ginseng in Treating Alzheimer’s Disease Based on Network Pharmacology

摘要: 目的：通过网络药理学与分子对接技术探究人参治疗阿尔茨海默病(Alzheimer’s disease, AD)的作用机制。方法：通过TCMSP数据库筛选人参的活性成分，用PubChem数据库对人参活性成分进行筛选，得到人参活性成分的靶点。通过GeNET数据库和GeneCards数据库提取阿尔茨海默病发病机制相关的靶点，将两个数据库得到的靶点取交集绘制Venn图，得到最终的疾病靶点，并与人参主要成分靶点进行映射，得到药物–疾病互作靶点。通过String数据库绘制蛋白质–蛋白质相互作用(protein-protein interaction, PPI)网络，使用Cytoscape软件构建药物–疾病互作靶点网络，采用DAVID v6.8在线分析平台对关键靶点进行基因本体(gene ontology, GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析，利用Cytoscape软件将富集分析结果可视化并将分析所得关键化合物及靶点进行分子对接。利用孟德尔随机化分析调查互作靶点与阿尔茨海默病之间潜在的因果关系；结果：筛选出人参的活性成分有8个，活性成分对应靶点361个，活性成分靶点与疾病靶点取交集得到最终靶点121个。GO功能富集分析结果显示，人参可通过多靶点–多通路作用于阿尔茨海默病。KEGG通路富集分析结果显示，人参治疗阿尔茨海默病主要包括神经活性配体–受体的相互作用、Ras、MAPK信号通路以及多种细胞凋亡通路。结论：通过网络药理学及分子对接技术揭示了人参治疗阿尔茨海默病的关键成分及作用靶点，这些发现为深入的研究人参的药理作用及开发新型阿尔茨海默病治疗药物奠定了理论基础。

Abstract: Objective: To explore the mechanism of ginseng in the treatment of Alzheimer’s disease (AD) through network pharmacology and molecular docking technology. Methods: The active components of ginseng were screened by the TCMSP database and screened by the PubChem database to get the target of ginseng active components. Targets related to the pathogenesis of Alzheimer’s disease were extracted from the GeNET database and GeneCards database, and the targets obtained from the two databases were intersected to draw a Venn diagram to obtain the final disease targets, and the targets of ginseng main components were mapped to obtain drug-disease interaction targets. The protein-protein interaction (PPI) network was mapped using the String database, and the drug-disease interaction target network was constructed using Cytoscape software. The gene ontology (GO) function and the Kyoto encyclopedia of genes and genomes (KEGG) pathway concentration analysis were conducted using the DAVID v6.8 online analysis platform. The results of the enrichment analysis were visualized by Cytoscape software and the key compounds and targets obtained from the analysis were interlinked. Mendelian randomization analysis was used to investigate the potential causal relationship between interaction targets and Alzheimer’s disease. Results: There were 8 active ingredients of ginseng, 361 targets corresponding to active ingredients, and 121 final targets were obtained by intersection of active ingredient targets and disease targets. GO functional enrichment analysis showed that ginseng could act on Alzheimer’s disease through multi-target-multi-pathway. The results of the KEGG pathway enrichment analysis showed that the treatment of ginseng for Alzheimer’s disease mainly included the interaction of neuroactive ligand-receptor, Ras, MAPK signaling pathways and various apoptosis pathways. Conclusion: Through network pharmacology and molecular docking technology, the key components and targets of ginseng in the treatment of Alzheimer’s disease were revealed, and these findings laid a theoretical foundation for further research on the pharmacological effects of ginseng and the development of novel drugs for the treatment of Alzheimer’s disease.