基于网络药理学探讨黄连温胆汤治疗失眠的机制

Mechanism of Huanglian Wendan decoction in treating insomnia based on network pharmacology

目的基于“胃不和则卧不安”理论,采用网络药理学的研究方法,探讨黄连温胆汤治疗失眠的作用机制。方法从不同年代的中药著作中收集黄连温胆汤的药物归经,并绘制表格;利用中药系统药理学数据库与分析平台(TCMSP)和Uniprot数据库检索并收集黄连温胆汤的有效成分和作用靶点,使用Cytoscape 3.7.2软件构建“药物-靶点-有效成分”网络图;在Genecards数据库收集“失眠症”的相关靶点,筛选出药物与疾病交集靶点,绘制交集靶点韦恩图;通过STRING数据库对交集靶点进行分析,借助Cytoscape 3.7.2软件构建蛋白相互作用(PPI)网络图;对药物干预疾病的作用靶点进行靶点基因本体(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,使用Cytoscape 3.7.2软件构建“核心靶点-通路”网络图。结果黄连温胆汤共涉及8味中药,药物归经主要为脾、胃、肺、心经,且其余各经均有涉及;共筛选出83个药物有效成分、124个靶点,其中有42个关键靶点与失眠症相关;PPI网络中共得到40个节点、428条相互作用关系的连线;按照P<0.05的标准,GO富集到51个基因功能,KEGG富集到35条基因通路。结论黄连温胆汤的药物归经具有脾、胃、心经的重点选择性;其主要化合物成分为槲皮素、川陈皮素、β-谷甾醇、柚皮苷、木犀草素等;主要作用于白细胞介素-6(IL-6)、细胞周期素D1(CCND1)、血管内皮生长因子A(VEGFA)、细胞间黏附分子-1(ICAM1)、低聚果糖(FOS)等核心靶点,以及核受体活性通路、神经递质结合通路、NF-κB信号通路等生物过程。黄酮类化合物及炎症因子的抗炎作用可能为黄连温胆汤治疗失眠的作用机制。

Objective To explore the mechanism of Huanglian Wendan decoction in treating insomnia based on the theory of"stomach disharmony causes restlessness in bed"and with the method of network pharmacology.Methods The classics of Huanglian Wendan decoction from Chinese medicine works of different ages was collected to draw a table;The active components and action targets of Huanglian Wendan decoction were retrieved and collected by TCMSP and Uniprot database.Cytoscape 3.7.2 software was used to construct the network diagram of"drug-targets-active components".Related targets of"insomnia"were collected from GeneCards database,and the intersection targets of drugs and diseases were screened out,and the Venn plot of intersection targets was drawn.The intersection targets were analyzed by the STRING database,and the PPI network map was constructed by Cytoscape 3.7.2 software.Target gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analy siswere carried out for drug intervention disease action targets.Cytoscape 3.7.2 software was used to construct the"core targets-pathway"network diagram.Results Huanglian Wendan decoction involves a total of 8 traditional Chinese medicines.The main drug meridians were spleen,stomach,lung and heart meridians,and the other meridians were involved.A total of 83 active ingredients and 124 targets were screened out,among which 42 key targets were related to insomnia.A total of 40 nodes and 428 interaction connections were obtained in PPI network.According to the standard of P<0.05,GO was enriched in 51 gene functions and KEGG in 35 gene pathways.Conclusion The drug meridian of Huanglian Wendan decoction has the key selectivity of spleen,stomach and heart meridian.Its main compounds were quercetin,tangerine peel,β-sitosterol,naringin,luteolin and so on.It mainly acts on core targets such as interleukin-6(IL-6),cyclin D1(CCND1),vascular endothelial growth factor A(VEGFA),intercellular adhesion molecule-1(ICAM1),fructose oligosaccharide(FOS),aswellas biological processes such as nuclear receptor activity pathway,neurotransmitter binding pathway,and NF-κB signaling pathway.The anti-inflammatory effect of flavonoids and inflammatory factors may be the mechanism of Huanglian Wendan decoction in the treatment of insomnia.