激光生物学报2025，Vol.34Issue(5)：426-441,16.DOI:10.3969/j.issn.1007-7146.2025.05.006
基于网络药理学和代谢组学技术研究开心散治疗阿尔茨海默病的作用机制
Exploring the Mechanism of Kaixinsan in the Treatment of Alzheimer's Disease Based on Network Pharmacology and Metabolomics
摘要
Abstract
This study combined network pharmacology and hippocampal metabolomics to explore the active components and mechanism of kaixinsan(KXS)in treating Alzheimer's disease(AD).APP/PS1 male mice were used as the AD model.The morris water maze test was performed to evaluate learning and memory abilities,and hematoxylin-eosin(HE)staining was conducted to observe pathological changes in the hippocampal CA1 region.Through network pharmacology,common targets between KXS components in hippocampus and AD-related targets were identified,followed by gene ontology(GO)analysis,Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis,protein-protein interaction(PPI)network construction and molecular docking.Hippocampal metabolites were detected using liquid chromatography-tandem mass spectrometry(LC-MS/MS),and differential metabolites were screened for metabolic pathway enrichment analysis.Finally,comprehensive analysis was performed by integrating network pharmacology and metabolomics results.The morris water maze test shows that KXS improves learning and memory abilities in APP/PS1 mice.HE staining results indicate that KXS ameliorates central nervous system damage.LC-MS/MS identifies 466 KXS-derived compounds in hippocampus and 87 potential therapeutic targets.The main KEGG enriched pathways include lipid and atherosclerosis,efferocytosis,and AD pathways.Molecular docking results demonstrate high binding affinity between KXS potential active components and key targets.A total of 501 differential metabolites are screened from hippocampus,enriching 6 metabolic pathways.Integrated analysis of network pharmacology and metabolomics pathways yields intersecting pathways including linoleic acid metabolism and cholinergic synapse.This study reveals that KXS components in hippocampus can target AD-related disease targets,which are associated with pathways such as linoleic acid metabolism and cholinergic synapse.These findings may explain the potential mechanism of KXS in treating AD.关键词
阿尔茨海默病/开心散/网络药理学/代谢组学/分子对接Key words
Alzheimer's disease/kaixinsan/network pharmacology/metabolomics/molecular docking分类
中医学引用本文复制引用
李子璇,张丽艳,闵冬雨,刘勇明,程美佳,袁常斌,鞠业涛,杨雅丽,何晓明,于畅洋,张力..基于网络药理学和代谢组学技术研究开心散治疗阿尔茨海默病的作用机制[J].激光生物学报,2025,34(5):426-441,16.基金项目
国家自然科学基金面上项目(82174114) （82174114）
辽宁省教育厅2024年度高等学校基本科研项目(LJ222410162045) （LJ222410162045）
沈阳市科技计划项目(20-205-4-008). （20-205-4-008）
