基于网络药理学探讨柴胡异病同治功能性便秘合并睡眠障碍的作用机制

The action mechanism of radix bupleuri on functional constipation plus sleep disorder based on network pharmacology

目的:运用网络药理学方法探讨柴胡“异病同治”功能性便秘合并睡眠障碍的作用靶点及可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索柴胡的所有化学成分并筛选作用靶点,通过GeneCards、OMIM数据库查询功能性便秘及睡眠障碍的疾病靶点;利用函数公式筛选药物和疾病的交集靶点,借助String数据库构建靶点蛋白质相互作用网络;通过Cytoscape 3.8.0软件构建中药-化学成分-疾病靶点网络;利用Metascape数据库对靶基因进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选出5个主要化学成分,10个关键靶点,基因富集分析得到1427条GO功能条目和241条KEGG通路。结论:柴胡治疗功能性便秘及睡眠障碍可能涉及以丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、趋化因子CCL2(C-C Motif Chemokine Ligand 2,CCL2)等核心靶点为代表,其异病同治的机制可能与调控AGE-RAGE信号通路、癌症相关通路、缺氧诱导因子-I(Hypoxia Inducible Factor-I,HIF-1)信号通路、多巴胺能突触、p53信号通路、昼夜节律等信号通路等有关。

Objective:To explore the targets and possible action mechanisms of radix bupleuri on functional constipation plus sleep disorder based on network pharmacology.Methods:The chemical components and targets of radix bupleuri were retrieved from TCMSP,and diseases targets of functional constipation plus sleep disorder were queried from GeneCards database and OMIM database.The intersection targets of medicines and diseases were screened by function formula,and a target protein-protein interaction network was constructed by String database.The traditional Chinese medicine-chemical compositions-diseases targets network was constructed by Cytoscape 3.8.0 software.The GO enrichment analysis and KEGG pathway enrichment analysis of targets was performed by Metascape database.Results:Five main chemical components and ten key targets were screened out,and 1427 GO functional items and 241 KEGG pathways were obtained from gene enrichment analysis.Conclusion:Radix bupleuri on functional constipation plus sleep disorder may involve in core targets such as AKT1,VEGFA,IL-6,TNF and CCL2.Its mechanism of treating different diseases by same method may be related to the regulation of AGE-RAGE signaling pathway,pathways in cancer,HIF-1 signaling pathway,dopaminergic synapse,p53 signaling pathway,circadian entrainment and other signaling pathways.