摘要
目的:运用网络药理学和分子对接分析枳实-白芍药对镇痛的作用机制。方法:利用中药系统药理学数据库和分析平台检索枳实、白芍的有效成分及对应靶点,GeneCards、DisGeNet以及OMIM数据库检索疼痛相关基因靶点,取两者交集靶点,借助STRING数据库构建蛋白互作网络图,应用Cytoscape3.9.1软件筛选核心靶点,构建“药物-成分-靶点”网络图。通过DAVID数据库对共同靶点进行GO和KEGG通路富集分析。通过AutoDock 1.5.7对主要成分和核心靶点进行分子对接。结果:经筛选获得药物有效成分16个,药物与疾病共同靶点75个,其中肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleukin-6,IL-6)、丝氨酸/苏氨酸蛋白激酶1(serine/threonine-protein kinase 1,AKT1)、血管内皮生长因子A(vascular endothelial growth factorA,VEGFA)、肿瘤蛋白P53(tumor protein P53,TP53)等17个核心靶点可能是枳实-白芍药对镇痛的关键靶点。GO生物学过程主要涉及基因表达正调控、对外源性刺激的反应、脂多糖介导的信号通路等,KEGG信号通路主要涉及TNF信号通路、磷脂酰肌醇3-激酶(phosphoinositide 3 kinase,PI3K)/丝氨酸-苏氨酸激酶(serine-threonine kinase,Akt)信号通路、癌症通路等。分子对接结果显示主要成分与核心靶点结合较好。结论:枳实-白芍药对中的木犀草素、山柰酚、柚皮素等有效成分可能通过作用于TNF、IL-6、AKT1、VEGFA、TP53等靶点来调节TNF信号通路、PI3K-Akt信号通路、癌症通路等通路发挥镇痛作用。
Objective:To explore the analgesic mechanism of Zhishi-Baishao drug pair in the treatment of pain by network pharmacology and molecular docking.Methods:The TCMSP database was used to search for the effective components and targets of Zhishi-Baishao drug pair.GeneCards,DisGeNet and OMIM database were used to obtain the pain related targets.The intersection targets of the two were selected and imported into the STRING database to construct protein-protein interaction network.Then the core targets were screened out and the"drug-component-target"network diagram was drawn by Cytoscape3.9.1 software.GO and KEGG pathway enrichment analysis were performed through the DAVID database.Finally,AutoDock 1.5.7 was used to verify the molecular docking of the main effective components with the core targets.Results:A total of 16 effective components and 75 intersection targets between drug and disease were screened out.Among them,17 core targets may be key targets for analgesic effect,including tumor necrosis factor(TNF),interleukin-6(IL-6),serine/threonine-protein kinase 1(AKT1),vascular endothelial growth factor A(VEGFA),tumor protein P53(TP53)and so on.The biological processes derived from GO analysis mainly involved positive regulation of gene expression,response to xenobiotic stimulus,lipopolysaccharide-mediated signaling pathway.KEGG signaling pathways mainly involved TNF signaling pathway,Phosphoinositide 3 kinase(PI3K)/serine-threonine kinase(Akt)signaling pathway,and pathways in cancer.Molecular docking showed good binding between the main active components and the core targets.Conclusion:The effective components such as luteolin,kaempferol,naringenin in Zhishi-Baishao drug pair may regulate TNF signaling pathway,PI3K-Akt signaling pathway,and pathways in cancer by acting on targets such as TNF,IL-6,AKT1,VEGFA,and TP53,and exert analgesic effects.
作者
刘春华
樊碧发
张媛婧
胡慧敏
李晨
李怡帆
张毅
毛鹏
LIU Chun-hua;FAN Bi-fa;ZHANG Yuan-jing;HU Hui-min;LI Chen;LI Yi-fan;ZHANG Yi;MAO Peng(Department of Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Pain Medicine,China-Japan Friendship Hospital,Beijing 100029,China)
出处
《中国疼痛医学杂志》
CAS
CSCD
北大核心
2024年第7期501-508,514,共9页
Chinese Journal of Pain Medicine
基金
中日友好医院高水平医院临床业务费专项临床研究项目(2022-NHLHCRF-YSPY-02)
国家重点研发计划(2016-KJBYF-004)
首都卫生发展科研专项项目(首发2022-1-4061)。
关键词
枳实
白芍
疼痛
网络药理学
分子对接
zhishi
baishao
pain
network pharmacology
molecular docking
