摘要
目的:通过网络药理学以及分子对接探讨姜黄素治疗卒中后抑郁的潜在分子作用机制.方法:运用人类基因综合数据库(GeneCards)、药物基因组知识库(PharmGKB)、瑞士靶点数据库(SwissTargetPrediction)检索姜黄素潜在作用靶点;通过在线人类孟德尔遗传数据库、GeneCards数据库检索缺血性脑卒中和抑郁的潜在靶点.利用蛋白质数据库(Uniprot)对靶点进行规范,随后导入韦恩(Venn)在线平台,得到三者之间的交集靶点.通过基因间功能关联数据库(STRING)和Cytoscape 3.7.1软件对交集靶点进行蛋白相互作用(PPI)可视化分析;Metascape数据库对交集靶点进行基因本体(GO)和基因组百科全书(KEGG)通路富集分析.最后,利用AutoDock Vina1.5.6软件对姜黄素与核心靶点进行分子对接验证.结果:共获得缺血性脑卒中及抑郁潜在靶点1452个,药物作用靶点207个,三者的交集靶点47个.GO功能富集分析得到2332个条目,KEGG通路富集分析得到138个条目.根据度值大小及富集分数筛选出白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、白细胞介素-1β(1L-1β)等核心靶点及高级糖基化终末产物-受体(AGE-RAGE)信号通路、白细胞介素-17(IL-17)信号通路、TNF信号通路等.分子对接结果显示姜黄素与IL-6、TNF、AKT1、IL-1β等核心靶点有较强的结合能力.结论:姜黄素可能作用于IL-6、TNF、AKT1、IL-1β等关键靶点,通过AGE-RAGE、IL-17、TNF等信号通路发挥重要作用.
Abstract
Objective:To explore the potential molecular mechanism of curcumin in the treatment of post-stroke depression through network pharmacology and molecular docking.Methods:The potential targets of curcumin were searched in GeneCards,PharmGKB and SwissTargetPrediction database.The online Mendelian Inheritance in Man data-base and GeneCards database were searched for potential targets of ischemic stroke and depression.The targets were standardized by Uniprot and then imported into Venn online platform to obtain the intersection targets among the three.Protein-protein interaction(PPI)was visualized by STRING and Cytoscape 3.7.1 software.Metascape database was used to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of intersection targets.Finally,AutoDock Vina1.5.6 software was used to verify the molecular docking between curcumin and core targets.Results:A total of 1452 potential targets for ischemic stroke and depression,207 drug tar-gets,and 47 intersection targets of the three were obtained.GO functional enrichment analysis yielded 2332 items,and KEGG pathway enrichment analysis yielded 138 items.According to the degree value and enrichment fraction,the core targets such as interleukin-6(IL-6),tumor necrosis factor(TNF),serine/threonine protein kinase 1(AKT1),inter-leukin-1β(IL-1β)and the advanced glycation end products receptor(AGE-RAGE)signaling pathway,interleukin-17(IL-17)signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that curcumin had a strong binding ability to core targets such as IL-6,TNF,AKT1,and 1L-1β.Conclusion:Curcumin may act on key targets such as IL-6,TNF,AKT1,IL-1β,and play an important role through the AGE-RAGE,IL-17,and TNF signaling pathways.
基金项目
云南省教育厅科学研究基金研究生类项目(2023Y0793)
昆明医科大学硕士研究生创新基金(2023S005)
维普
万方数据