摘要
目的:基于网络药理学及分子对接技术探讨人参-茯苓药对治疗阿尔茨海默病(AD)的潜在作用机制。方法:利用中药系统药理学技术平台(TCMSP)等数据库,以口服生物利用度(OB)和类药性(DL)为条件预测及筛选人参-茯苓活性成分。通过GeneCards数据库收集与治疗AD相关的作用靶点;运用DAVID数据库及Cytoscape 3.8.2软件构建成分-靶点、靶点蛋白互作网络图;对靶点基因进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析;将药理网络中的核心成分及核心靶点进行分子对接。结果:利用TCMSP数据库分析得到人参-茯苓药对中的活性成分主要有山柰酚、β-谷甾醇、豆甾醇等,可作用于以肿瘤坏死因子(TNF)、过氧化物酶体增殖活性受体γ(PPARG)、白细胞介素-1β(IL-1β)、一氧化氮合酶3(NOS3)、JUN原癌基因(JUN)等为主的76个与AD相关的靶点;主要通过神经活性配体-受体相互作用通路、钙信号通路、胆碱能突触、多巴胺能突触等79条信号通路,参与胆碱突触能传递、对药物的反应、乙酰胆碱相关受体、细胞增殖的正向调节等215个生物过程,进一步发挥药效。分子对接结果显示,筛选的主要活性成分与重要靶点结合活性较好。结论:人参-茯苓药对治疗AD具有多成分、多途径和多靶点的特点。
Objective:To explore the mechanisms of Ginseng-Poria medicinal combination for the treatment of Alzheimer's disease(AD)Based on network pharmacology and molecular docking technology.Methods:The active components of Ginseng-Poria medicinal combination were predicted and screened under the conditions of oral bioavailability(OB)and drug-likeness(DL)using the Traditional Chinese Medicine System Pharmacology Technology Platform(TCMSP).The action targets related to the treatment of AD were collected through the GeneCards database.The component-target and target-protein interaction network diagrams were constructed using the DAVID database and Cytoscape 3.8.2 software.The target genes were analyzed for gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and the core components and core targets in the pharmacological network were subjected to molecular docking.Results:The active components in Ginseng-Poria medicinal combination were analyzed using the TCMSP database,mainly including kaempferol,β-sitosterol,and stigmasterol.It acted on 76 targets related to AD,including tumor necrosis factor(TNF),peroxisome proliferative activity receptorγ(PPARG),interleukin-1β(IL-1β),nitric oxide synthase 3(NOS3),and JUN proto-oncogene(JUN),through 79 the neuroactive ligand-receptor interaction pathway,calcium signaling pathway,cholinergic synapses,and dopaminergic synapses.It participated in 215 biological processes including cholinergic synaptic energy transmission,drug response,acetylcholine-related receptors,and positive regulation of cell proliferation,exerting the therapeutic effect.The results of molecular docking showed that the main active ingredients screened with better binding activity and the important targets.Conclusion:Ginseng-Poria medicinal combination for treating AD showed the characteristics of multiple components,multiple pathways,and multiple targets.
作者
周梦玲
王燕丽
于博睿
ZHOU Mengling;WANG Yanli;YU Borui(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300073,China)
出处
《中西医结合心脑血管病杂志》
2025年第14期2112-2120,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
北京中医医院院级课题暨两院合作课题项目(No.LYYB202219)
北京中医药大学教育科学研究课题项目(No.XJY21103)。
关键词
阿尔茨海默病
人参-茯苓药对
网络药理学
分子对接
作用机制
Alzheimer's disease
Ginseng-Poria medicinal combination
network pharmacology
molecular docking
mechanism
作者简介
通讯作者:于博睿,E-mail:yu_borui@163.com。
