基于网络药理学和分子对接技术探索人参活性成分治疗阿尔茨海默病的作用机制

Based on Network Pharmacology and Molecular Docking Technology, Exploring the Mechanism of Action of Ginseng Active Ingredients in the Treatment of Alzheimer’s Disease

摘要: 目的：本研究旨在通过网络药理学和分子对接技术，探索人参活性成分治疗阿尔茨海默病(Alzheimer’s disease, AD)的作用机制。方法：通过中药系统药理学数据库(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)筛选人参的活性成分及其靶点，并结合基因表达综合数据库(Gene Expression Omnibus, GEO)和在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man, OMIM)获取AD相关靶点。再利用DAVID数据库进行基因本体(Gene Ontology, GO)功能富集分析和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，揭示人参治疗AD的潜在生物学功能和信号通路。最后，通过分子对接技术验证人参活性成分与AD关键靶点的相互作用。结果：研究筛选出53个人参治疗AD的潜在靶点，GO富集分析显示这些靶点主要参与神经信号传导、细胞迁移和线粒体功能等生物学过程。KEGG通路分析表明，人参活性成分显著富集于TNF信号通路、IL-17信号通路和AGE-RAGE通路等与AD相关的炎症和代谢调控通路。分子对接结果显示，人参皂苷Rg2、β-谷甾醇等活性成分与AKT1、TNF、IL1B等关键靶点具有较强亲和力(结合能 ≤ −6.0 kcal/mol)，提示其可能通过抑制炎症反应、调节细胞凋亡和改善能量代谢发挥治疗作用。结论：本研究揭示了人参通过多靶点、多通路调控炎症反应、线粒体功能和神经信号传导干预AD的潜在机制，为人参治疗AD提供了新的理论依据。研究结果支持人参活性成分在AD治疗中的潜在应用，并为中药复方的机制解析提供了可借鉴的技术路线。

Abstract: Objective: To explore the mechanism of action of ginseng active ingredient in the treatment of Alzheimer’s disease (AD) through network pharmacology and molecular docking technology. Methods: The active ingredients and targets of ginseng were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and combined with the Gene Expression Omnibus (TCMSP, GEO) and the Online Mendelian In-heritance in Man (OMIM) to obtain AD-related targets. The DAD database was used to analyze the functional enrichment of Gene Ontology (GO) and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the potential biological functions and signaling pathways of ginseng in the treatment of AD were revealed. Finally, the interaction between ginseng active ingredients and key AD targets was verified by molecular docking technology. Results: A total of 53 potential ginseng targets for the treatment of AD were screened, and GO enrichment analysis showed that these targets were mainly involved in biological processes, such as nerve signaling, cell migration, and mitochondrial function. KEGG pathway analysis showed that the active ingredients of ginseng were significantly enriched in the inflammatory and metabolic regulatory pathways related to AD, such as TNF signaling pathway, IL-17 signaling pathway and AGE-RAGE pathway. The results of molecular docking showed that the active ingredients such as ginsenoside Rg2 and β-sitosterol had strong affinity (binding energy of ≤−6.0 kcal/mol) with key targets such as AKT1, TNF and IL1B, suggesting that they may play a therapeutic role by inhibiting inflammatory response, regulating apoptosis and improving energy metabolism. Conclusion: This study reveals the potential mechanism of ginseng intervention in AD through multi-target and multi-pathway regulation of inflammatory response, mitochondrial function and nerve signaling, and provides a new theoretical basis for ginseng in the treatment of AD. The results of this study support the potential application of ginseng active ingredients in the treatment of AD, and provide a technical route for the mechanism analysis of TCM compounds.