摘要
目的使用网络药理学和分子对接方法探究红花黄色素延缓衰老作用。方法利用PubChem、PharmMapper、SwissTargetPrediction和TargetNet数据库查询红花黄色素相关基因;借助Uniprot数据库查询红花黄色素化合物对应基因名称;Cytoscape 3.9.0构建化合物-靶点网络;通过GeneCards、OMIM、TTD、DisGeNET和DrugBank数据库筛选衰老相关基因;取交集获取红花黄色素-衰老共同基因;利用R软件(clusterProfiler包)和微生信平台对交集靶点基因进行GO和KEGG通路富集分析;采用Cytoscape 3.9.0软件进行化合物-靶点-通路网络构建与可视化分析;绘制蛋白互作(protein proteininteraction,PPI)网络并获取核心基因;通过TRRUST和MetaScape数据库进行转录因子及相关调控基因富集;利用LeDock和PyMOL软件对化合物与核心靶点基因行分子对接;最后,利用DisGeNET数据库获取靶点类型信息。结果得到386个红花黄色素作用相关基因,913个衰老相关基因,两者交集靶点共71个。富集分析显示共涉及129条信号通路及1519种生物过程、107种分子功能、71种细胞组分;靶点主要涉及糖尿病并发症中的AGE-RAGE信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路、癌症蛋白聚糖通路、MAPK信号通路,获得STAT3、PIK3CA、TP53、EP300、VEGFA、EGFR、PTPN11、JUN、CCND1和PTPN110个节点基因、53个相关转录因子;分子对接显示,红花黄色素4种化合物SYA、SYB、HSYA、AHSYB与核心靶点之间均具有稳定的结合能力;作用靶点类型主要涉及激酶、转录因子、信号分子、核酸结合蛋白、酶调制器等类型。结论红花黄色素抗衰老的作用是多靶点和多途径的,与衰老相关靶点共有71个交集靶基因,对这些靶基因进行GO功能富集分析,发现红花黄色素延缓衰老的基因功能;并进行KEGG通路富集分析,发现红花黄色素延缓衰老是一个多重复杂的过程,并且通过调节多个信号通路共同发挥作用。这为实验室�
Objective To explore the mechanism of safflor yellow in delaying aging by network pharmacology and molecular docking techniques.Methods Safflor yellow(SY)related gene targets were inquired through PubChem,Pharm Mapper,Swiss Target Prediction and Target Net database,Uni-Prot Database were used for searching the corresponding compounds’names.The compound-target network was built by Cytoscape390.The aging related genes targets were identified used Gene Cards,OMIM,TTD,DisGeNET and DrugBank database.Access to SY-aging related genes.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis of interested target genes were performed in R software(clusterProfiler)to investigate the molecular mechanisms.Cytoscape software was used to construct and visualized the compound target-pathway network.The protein-protein interaction network was drawn to obtain hub genes.The transcription factors and related regulatory genes were specifically enriched by TRRUST and Metascape database.Molecular docking verification of compound and hub target genes was conducted using LeDock and PyMOL software.Afterward,the targets type was attributed by DisGeNET database.Results In this study,386 targets of Safflor yellow were predicted,913 senescence targets were collected and 71 intersection targets.The results of enrichment analysis showed that a total of 129 signaling pathways and 1519 biological processes,107 molecular functions and 71 cellular components were involved.Which mainly involving AGE-RAGE,PI3K-Akt,proteoglycans in cancer and MAPK pathways.10 hub genes including STAT3,PIK3,CA,TP53,EP300,VEGFA,EGFR,PTPN11,JUN,CCND1 and PTPN1 were identified by protein protein interaction(PPI)analysis.53 related transcription factors were probed,Molecular docking showed that all compounds have stable binding ability to core targets.The type of target was mainly related to kinase,transcription factors,signaling,nucleic acid binding protein and enzyme.Conclusion The anti-aging effect of safflor yellow is multi-target and multi
作者
金雪
刘梓璇
刘洋
桂金秋
唐小云
石学魁
JIN Xue(Mudanjiang Medical University,Mudanjiang 157011,Heilongjiang,China)
出处
《牡丹江医学院学报》
2024年第2期1-9,共9页
Journal of Mudanjiang Medical University
基金
牡丹江医学院博士科研启动基金项目(2021-MYBSKY-013)。
关键词
红花黄色素
衰老
网络药理学
分子对接
信号通路
Safflor yellow aging
network pharmacology
molecular docking
Signal pathways
