摘要
目的基于网络药理学探讨小柴胡汤治疗胃食管反流病(GERD)合并失眠的潜在作用机制。方法通过在线数据库筛选小柴胡汤的活性成分、药物靶点以及GERD和失眠的疾病靶点;取药物靶点和疾病靶点的交集,利用STRING数据库分析交集靶点的相互作用;通过Cytoscape软件构建和分析“活性成分-靶点”“药物-活性成分-共同靶点-疾病”、蛋白质相互作用(PPI)网络;通过DAVID数据库对交集靶点进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析;通过BioGPS对核心靶点进行基因定位,结合Cytoscape构建“成分-靶点-通路-器官/组织”网络;使用AutoDockVina进行主要活性成分与核心靶点的分子对接。结果小柴胡汤治疗GERD合并失眠的主要活性成分包括槲皮素、山奈酚、黄芩素等多种化合物,关键靶点包括丝氨酸/苏氨酸激酶1(AKT1)、白细胞介素-1B(IL-1B)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、肿瘤蛋白53(TP53)等,与RNA聚合酶Ⅱ启动子转录的正调控、炎症应答、信号转导等生物过程相关,涉及的通路包括癌症途径、AGE-RAGE信号通路、TNF信号通路、MAPK信号通路等,关键基因定位于胰岛、胰腺、松果体、胸腺以及相关免疫细胞。分子对接结果表明,槲皮素能够与核心靶点结合并展现出较稳定的构象。结论小柴胡汤可能通过调控炎症免疫、糖脂代谢、昼夜节律而发挥治疗GERD合并失眠的作用。
Objective To elucidate the potential mechanism of Xiaochaihutang(XCHT)in treating gastroesophageal reflux disease(GERD)with insomnia by using network pharmacology.Methods The active ingredients and drug targets of Xiaochaihutang,diseases targets of GERD and insomnia were screened through online databases.The intersection of drug targets and disease targets was taken,and the interaction of the intersection targets was analyzed using STRING database.The"active ingredient-target""drug-active ingredient-common target-disease"and protein-protein interaction(PPI)networks were constructed and analyzed by Cytoscape software.Gene ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection targets by the DAVID database.Gene localization of core targets was performed by BioGPS,and the"ingredient-target-pathway-organ/tissue"network was constructed by Cytoscape.AutoDock Vina was used for the molecular docking of main active components with core targets. Results The main active ingredients of Xiaochaihutang in the treatment of GERD complicated with insomnia included Quercetin,Kaempferol,Baicalein and other ingredients.The key targets included serine/threonine kinase 1(AKT1),interleukin-1B(IL-1B),interleukin-6(IL-6),tumor necrosis factor(TNF),tumor protein 53(TP53)and so on,which were related to the positive regulation of RNA polymeraseⅡpromoter transcription,inflammatory response,signal transduction,and other biological processes.The involved pathways included cancer pathway,AGE-RAGE signaling pathway,TNF signaling pathway and MAPK signaling pathway and so on.Key genes were located in the islet,pancreas,pineal gland,thymus and related immune cells.Molecular docking results showed that Quercetin could bind to the core target and exhibit stable conformation.Conclusion Xiaochaihutang may play a role in the treatment of GERD complicated with insomnia by regulating inflammatory immunity,glucose and lipid metabolism and circadian rhythm.
作者
蒲美旨
冯小可
谢立群
PU Meizhi;FENG Xiaoke;XIE Liqun(Department of Traditional Chinese Medicine,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu,210029;Institute of Integrative Traditional Chinese and Western Medicine,Nanjing Medical University,Nanjing,Jiangsu,210029)
出处
《实用临床医药杂志》
CAS
2023年第9期111-118,共8页
Journal of Clinical Medicine in Practice
基金
国家自然科学基金青年科学基金资助项目(81801625)。
关键词
小柴胡汤
胃食管反流病
失眠
网络药理学
分子对接
炎症
Xiaochaihutang
gastroesophageal reflux disease
insomnia
network pharmacology
molecular docking
inflammation
