天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (10): 1787-1799.doi: 10.16333/j.1001-6880.2024.10.015

• 数据研究 • 上一篇    下一篇

基于UPLC-Q-TOF-MS/MS及网络药理学探讨多裂骆驼蓬治疗阿尔茨海默病的有效成分和作用机制

程亚敏,黄丹蓉,任静玉,冯紫涵,周文斌,申刚义*   

  1. 中央民族大学药学院 民族医药教育部重点实验室(中央民族大学),北京 100081
  • 出版日期:2024-10-28 发布日期:2024-10-28
  • 基金资助:
    国家自然科学基金(82374161);民族医药教育部重点实验室(中央民族大学)自主课题(KLEM-ZZ202302);中央民族大学研究生课程思政示范课培育项目(GRSKCS005)

Effective components and mechanism of Peganum multisectum in the treatment of Alzheimer′s disease based on UPLC-Q-TOF-MS/MS and network pharmacology

CHENG Ya-min,HUANG Dan-rong,REN Jing-yu,FENG Zi-han,ZHOU Wen-bin,SHEN Gang-yi*   

  1. Key Laboratory of Ethnomedicine,Ministry of Education (Minzu University of China), School of Pharmacy,Minzu University of China,Beijing 100081,China
  • Online:2024-10-28 Published:2024-10-28

摘要:

本研究通过超高效液相色谱-四极杆飞行时间串联质谱法(UPLC-Q-TOF-MS/MS)、网络药理学及分子对接技术探讨多裂骆驼蓬抗阿尔茨海默病(Alzheimer′s disease,AD)药效物质基础及作用机制。利用 UPLC-Q-TOF-MS/MS技术对多裂骆驼蓬进行定性研究;结合质谱分析结果,利用SWISS ADME、GeneCards等数据库筛选多裂骆驼蓬活性成分、对应靶点及疾病靶点;利用Venn绘制平台获取交集靶点,并导入STRING在线分析平台和Cytoscope3.9.1软件,进行蛋白质相互作用分析,构建药物-成分-靶点网络;利用AlzDate数据库差异表达模块分析靶点的表达与β-淀粉样蛋白(β-amyloids,Aβ)和微管相关蛋白(Tau)相关病理学的关系;通过DAVID数据库进行GO和KEGG通路富集分析;利用Autodock Vina软件实现核心靶点与有效成分分子对接模型的构建。从多裂骆驼蓬中共鉴定出34个主要成分,包括生物碱类10种,黄酮类5种,氨基酸类5种,萜类5种,核苷类2种,酚酸类3种,其他类化合物4种。网络药理学分析结果显示,吴茱萸碱、β-谷甾醇、β-豆甾醇酮和去氢骆驼蓬碱等活性成分可通过作用靶点调节一系列与AD发病机制相关的生物学过程、分子功能和信号通路,进而调节胆碱能系统和功能、减少Aβ损伤、调节微循环及神经元结构和功能发挥治疗AD的作用。分子对接显示有效成分吴茱萸碱、β-谷甾醇、β-豆甾醇酮和去氢骆驼蓬碱与核心靶点MAPK3和STAT3均具有良好的结合活性。该研究初步揭示了多裂骆驼蓬治疗AD的药效物质基础及作用机制,为临床应用和药物开发提供了依据。 

关键词: 多裂骆驼蓬, 阿尔茨海默病, UPLC-Q-TOF-MS/MS技术, 网络药理学

Abstract:

This study explored the pharmacodynamic material basis and mechanism of action of Peganum multisectum (Maxim.) Mobr.in treating Alzheimer′s disease (AD) through ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS),network pharmacology,and molecular docking techniques.Based on UPLC-Q-TOF-MS/MS to analyze the main components of P. multisectum; Combined with the MS results,the active components of P. multisectum,corresponding target proteins,and disease targets were screened using databases such as SWISS ADME and GeneCards.Venn diagram analysis was performed to obtain intersected targets,which were then imported into Cytoscape 3.9.1 software and the STRING online analysis platform for protein-protein interaction analysis and construction of a drug-ingredient-target network.The relationship between the expression of core targets and the pathology of β-amyloids (Aβ) and microtubule associated protein (Tau) was analyzed using the differentially expressed module of the AlzDate database.GO and KEGG pathway enrichment analysis were conducted using the DAVID database;Autodock Vina software was utilized to construct molecular docking models between core targets and active components.A total of thirty-four major components were identified from P. multisectum,including ten alkaloids,five flavonoids,five amino acids,five terpenes,two nucleosides,three phenolic acids,and four other compounds.Network pharmacology analysis results showed that major active components such as evodiamine,β-sitosterol,β-stigmastenone,and harmine can regulate a series of biological processes,molecular functions,and signaling pathways related to the pathogenesis of AD by acting on targets,thereby regulating cholinergic system and function,reducing Aβ damage,regulating microcirculation and neuronal cell system and function for the treatment of AD.The results of molecular docking showed that evodiamine,β-sitosterol,β-stigmastenone,and harmine had good affinities to core targets such as MAPK3 and STAT3.This study preliminarily reveals the therapeutic effects and mechanisms of P. multisectum in the treatment of AD,providing a basis for clinical application and drug development.

Key words: Peganum multisectum, Alzheimer′s disease, UPLC-Q-TOF-MS/MS technology, network pharmacology

中图分类号:  R917