摘要
目的基于网络药理学探讨白藜芦醇治疗创伤性颅脑损伤(TBI)的作用机制。方法检索TCMSP、BATMAN-TCM、SuperPred、PharmMapper、SwissTargetPrediction和Drugbank数据库筛选获得白藜芦醇作用靶点577个,检索TTD、Drugbank、CTD、GeneCards、OMIM和Malacards数据库获得TBI相关靶点1100个,利用UniProt数据库获得交集靶点(即白藜芦醇治疗TBI的作用靶点)165个,构建药物-靶点-疾病网络。采用STRING数据库构建蛋白互作网络(PPI)。采用Metascape数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。采用AutoDockTools 1.5.6、Pymol 2.4.0、DiscoveryStudio 2020软件进行白藜芦醇与核心靶点的分子对接分析。结果165个交集靶点中,PPI排名前10的节点(即核心靶点)包括胰岛素(INS)、胰岛素样生长因子1、肿瘤坏死因子、TP53、白蛋白、白细胞介素(IL)-6、SRC、信号转导和转录活化因子3、血管内皮生长因子A、基质金属蛋白酶(MMP)-9。交集靶点的GO富集分析显示,生物过程主要涉及转移酶活性的正调控、细胞迁移的积极调控、活性氧代谢过程、对受伤的反应、内皮细胞增殖等;分子功能主要涉及激酶结合、蛋白激酶活性、蛋白磷酸酶结合、细胞因子受体结合、蛋白酶结合、转录因子结合等;细胞组分主要涉及膜筏、囊泡腔、突触后膜、树突、内质网腔、细胞间连接等。交集靶点的KEGG富集分析显示,信号通路主要涉及癌症途径、AGEs-RAGE信号通路、FoxO信号通路、补体与凝血级联等。分子对接显示白藜芦醇与IL-6、MMP-9、INS、SRC均有较好的结合活性。分子对接结果显示,白藜芦醇与10个核心靶点成功对接,其中白藜芦醇与IL-6、MMP-9、INS、SRC的对接结合能<-5 kJ/mol。结论白藜芦醇可能通过多靶点、多通路发挥减轻TBI和促进神经功能恢复的治疗作用。
Objective To explore the mechanism of resveratrol in the treatment of traumatic brain injury(TBI)based on network pharmacology.Methods Retrive TCMSP,BATMAN-TCM,SuperPred,PharmMapper,SwissTargetPrediction,and Drugbank databases to screen 577 targets of resveratrol.A total of 1100 TBI-related targets were obtained from TTD,Drugbank,CTD,GeneCards,OMIM,and Malacards databases,and 165 intersection targets(the targets of resveratrol for TBI)were obtained from the UniProt database to construct a drug-target-disease network.The STRING database was used to construct the protein-protein interaction(PPI)network.The Metascape database was used for the gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.AutoDockTools 1.5.6,Pymol 2.4.0,and DiscoveryStudio 2020 were used for molecular docking analysis of resveratrol with core targets.Results Among the 165 intersection targets,the top 10 PPI nodes(the core targets)included insulin(INS),insulin-like growth factor(IGF1),tumor necrosis factor,TP53,albumin(ALB),interleukin(IL)-6,SRC,signal transducer and transcription activator 3(STAT3),vascular endothelial growth factor A(VEGFA),and matrix metalloproteinase(MMP)9.GO enrichment analysis of the intersection targets showed that the biological processes mainly involved positive regulation of transferase activity,positive regulation of cell migration,reactive oxygen species metabolism process,response to injury,endothelial cell proliferation,etc.The molecular functions mainly involved kinase binding,protein kinase activity,protein phosphatase binding,cytokine receptor binding,protease binding,transcription factor binding,etc.The cellular components mainly involved membrane raft,vesicle lumen,postsynaptic membrane,dendrites,endoplasmic reticulum lumen,intercellular junction,etc.KEGG enrichment analysis of the intersection targets showed that the signaling pathways mainly involved the cancer pathways,AGEs-RAGE signaling pathway,FoxO signaling pathway,complement and coagulation cascades,etc.Molecular docking showed that resveratrol had a good binding activity with IL6,MMP9,INS,and SRC proteins.Molecular docking results showed that resveratrol has successfully docked with 10 core targets,among which the binding energy of resveratrol with IL-6,MMP9,INS,and SRC was less than-5 kJ/mol.Conclusion Resveratrol may exert therapeutic effects on alleviating TBI and promoting neurological recovery through multiple targets and multiple signaling pathways.
作者
刘飞飞
韩丽君
申友奎
陶开亮
LIU Feifei;HAN Lijun;SHEN Youkui;TAO Kailiang(Department of Neurosurgery,Hangzhou Hospital of Traditional Chinese Medicine,Affiliated to Zhejiang Chinese Medical University,Hangzhou 310007,China;不详)
出处
《心电与循环》
2023年第3期240-244,249,I0002,I0003,I0004,共9页
Journal of Electrocardiology and Circulation
基金
浙江省中医药科技计划项目(2021ZA105)。
作者简介
通信作者:申友奎,E-mail:shenyoukui@126.com。
