基于网络药理学和分子对接技术探讨补骨脂二氢黄酮甲醚治疗阿尔茨海默病的分子作用机制

Molecular Mechanism of Bavachinin in the Treatment of Alzheimer’s Disease Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学和分子对接技术探讨补骨脂二氢黄酮甲醚治疗阿尔茨海默病(AD)的分子作用机制。方法:通过Swiss Target Prediction数据库、PharmMapper数据库预测补骨脂二氢黄酮甲醚的作用靶点;分别在DisGeNET数据库、GeneCards数据库和Drugbank数据库检索获取AD相关靶点,再利用Venny 2.1.1绘制韦恩图获得两者共同靶点;将获得的两者共有靶点输入STRING数据库,构建共有靶点蛋白质-蛋白质相互作用(PPI)网络;再将PPI网络导入Cytoscape 3.7.2软件,利用其内置插件CytoHubba获取排序居前10位的关键靶点蛋白;利用R语言Cluster Profiler GO.R插件对关键靶点进行富集分析;使用AutoDock Vina软件将补骨脂二氢黄酮甲醚与核心靶点进行分子对接验证。结果:补骨脂二氢黄酮甲醚干预AD的核心靶点主要有丝裂原激活的蛋白激酶(MAPK)1、MAPK3、原癌基因酪氨酸蛋白激酶Src和胱天蛋白酶3(CASP3)等,主要涉及对活性氧的应答、肽基-丝氨酸磷酸化、肽基-丝氨酸修饰及细胞对化学应力的应答等生物过程,主要富集于雌激素、MAPK等信号通路。分子对接结果显示,补骨脂二氢黄酮甲醚与核心靶点蛋白MAPK1、MAPK3、SRC和CASP3均有较好的亲和力。结论:网络药理学预测了补骨脂二氢黄酮甲醚干预AD可能的作用靶点和信号通路,可为后续实验研究或药物开发提供理论基础和参考依据。

OBJECTIVE:To explore the molecular mechanism of bavachinin in the treatment of Alzheimer’s disease(AD)based on network pharmacology and molecular docking technology.METHODS:Target of bavachinin was predicted by Swiss Target Prediction database and PharmMapper database.DisGeNET,GeneCard and Drugbank databases were used to obtain the targets corresponding to AD.The common targets were queried by Venny 2.1.1 using Venn diagram,and the network of protein-protein Interaction(PPI)was constructed by inputting the two common targets into STRING database.Then the PPI network was imported into Cytoscape 3.7.2 software,and the top 10 key target proteins were obtained by its built-in plugin CytoHubba.Enrichment analysis were performed through Cluster Profiler GO.R plug-in for R language software.AutoDock Vina software was used for molecular docking of bavachinin and key targets.RESULTS:The core targets of bavachinin intervention in AD mainly included mitogen-activated protein kinase 1(MAPK1),MAPK3,SRC and caspase 3(CASP3),which were mainly involved in biological processes such as response to reactive oxygen species,peptide-serine phosphorylation,peptide-serine modification and cell response to chemical stress.Mainly concentrated in estrogen,MAPK and other signaling pathways.Results of molecular docking showed that bavachinin had good affinity with the key targets MAPK1,MAPK3,SRC and CASP3.CONCLUSIONS:Network pharmacology and molecular docking analysis predicts the possible targets and pathways of bavachinin in the treatment of AD,which provides theoretical basis and reference for subsequent experimental research or drug development.