神经药理学报 ›› 2024, Vol. 14 ›› Issue (5): 1-.DOI: 10.3969/j.issn.2095-1396.2024.05.001

• 研究论文 •    下一篇

基于网络药理学以及分子对接探讨白芍延缓阿尔茨海默症的作用机制

赵雨婷,殷宏艳,郭春燕   

  1. 河北北方学院药学院,河北省神经药理学重点实验室,张家口,075000,中国
  • 出版日期:2024-10-25 发布日期:2024-10-26
  • 通讯作者: 郭春燕,教授,硕士生导师;研究方向:体内药物分析和靶向药物分析;E-mail:guochy0311@163.com
  • 作者简介:赵雨婷,研究方向:药物分析;E-mail:2742432762@qq.com

Explore the Mechanism of Paeoniae Radix Alba Delaying Alzheimer's Disease Based on Network Pharmacology and Molecular Docking

ZHAO Yu-ting, YIN Hong-yan, GUO Chun-yan   

  1. Department of Pharmacy, Hebei North University, Hebei Key Laboratory of Neuropharmacology, Zhangjiakou, 075500, China
  • Online:2024-10-25 Published:2024-10-26

摘要:

目的:采用网络药理学和分子对接策略预测中药白芍延缓阿尔茨海默症(Alzheimer's disease,AD)的活 性成分、潜在作用靶点和机制,为白芍防治AD 的应用提供依据。方法:TCMSP 数据库用于查询白芍的化学成分 和靶点,通过Gene Cards 数据库查找AD 相关蛋白靶点,分别将白芍和AD 作用靶点,输入Venny 2.1.0 网站,得 到白芍与AD 的交集靶点,并绘制Venny 图,将交集靶点导入String 数据库下的Multiple proteins,绘制PPI 网络 图,再将交集靶点导入Cytoscape_v3.6.0,分析度值,筛选出度值排名靠前的化合物和靶点,并输出为活性化合物- 关键靶点网络图,后将交集靶点导入DAVID 网站,进行基因本体(gene ontology,GO)和(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析,最后采用分子对接技术验证白芍延缓AD 的作用靶点。结果:从白芍中筛选 出15 个化学成分,交集靶点208 个,GO 和KEGG 分析主要涉及到DNA 和RNA 缺陷、神经元功能障碍、病理性 蛋白质聚集、氧化应激、炎症反应。分子对接结果表明芍药苷(paeoniflorin,PF)、芍药内酯苷(albiflorin,AL)、儿 茶素[(+)-catechin,CT] 分别与HSP90AA1、SRC、EGFR 结合活性较好。:白芍能够通过抑制Aβ 蛋白的沉 积及Tau 蛋白的聚集、抑制炎症反应及氧化应激、保护神经元等达到延缓AD 的作用,其潜在分子机制可能是通 过白芍关键成分下调SRC、上调HSP90AA1 以及下调EGFR 实现,为白芍防治AD 的临床应用提供了新思路。

关键词: 网络药理学, 阿尔茨海默症, 分子对接, 白芍

Abstract:

Objective: To predict the active components, potential targets and mechanisms of Paeoniae Radix Alba in the prevention and treatment of Alzheimer's disease (AD) by network pharmacology and molecular docking strategy, so as to provide evidence for the application of Paeoniae Radix Alba in the prevention and treatment of AD. Methods: TCMSP database was used to query the chemical constituents and targets of Paeonia lactiflora and looked up the targets of AD-related proteins through Gene Cards database. Then, the targets of Paeoniae Radix Alba and AD were entered into Venny 2.1 website to get the intersection targets of root of herbaceous peony and AD, and made Venny map. The intersection targets were imported into Multiple proteins under String database, and the PPI network map was drawn. After importing the intersection targets into Cytoscape, the degree value was analyzed, and the top ranked compounds and targets were screened out. Then the intersection targets were imported into David website to conduct GO and KEGG analysis. Finally, the molecular docking technology was used to verify the Paeoniae Radix Alba in preventing and treating AD. Results: A total of 15 chemical constituents were screened from Paeoniae Radix Alba with 208 cross targets. The terms of GO and KEGG analysis mainly involved in RNA and DNA defect, protein binding, oxidative stress, inflammatory reaction and cancer-related pathways. The results of molecular docking showed that paeoniflorin (PF), albiflorin (AL) and Catechin [(+)-catechin, CT] bound SRC, EGFR and HSP90AA1 well, respectively. Conclusion: Paeoniae Radix Alba can prevent and treat AD by inhibiting the deposition of Aβ protein and the aggregation of Tau protein, inhibiting inflammatory reaction and oxidative stress, and protecting neurons. The underlying molecular mechanisms may be that PF, AL and CT down-regulates SRC, up-regulates HSP90AA1 and down-regulates EGFR. This paper provides a new idea for the clinical application of Paeoniae Radix Alba in the prevention and treatment of AD.

Key words: network pharmacology, Alzheimer's disease, molecular docking, Paeoniae Radix Alba

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