目的 基于网络药理学方法探讨栀子豉汤治疗抑郁、焦虑和失眠的作用机制。方法 筛选栀子豉汤活性成分;通过PharmMapper和CTD获取成分对应的靶点;将成分靶点与TTD、OMIM、DrugBank、CTD、Gene-Cards、DisGeNET数据库中获取的抑郁、焦虑和失眠疾病靶点分别取交集,将交集靶点分别导入String在线网站构建蛋白质相互作用网络,运用Cytoscape软件进行可视化分析,根据度值筛选出关键靶点;通过Matescape数据库对交集靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析;利用Cytoscape软件构建"成分-靶点-通路"网络,根据度值等筛选出核心活性成分。结果 共筛选19个活性成分,核心活性成分有大豆苷元、染料木素、栀子苷、芦丁、绿原酸等;活性成分和抑郁、焦虑和失眠疾病交集靶点分别为77、91、111个;KEGG通路富集分析结果显示,栀子豉汤治疗抑郁、焦虑和失眠主要涉及雌激素、丝裂原活化蛋白激酶、磷酸肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、叉头状转录因子(FOXO)、神经活性配体-受体相互作用、白细胞介素-17(IL-17)、多巴胺突触、糖尿病并发症中的晚期糖基化终产物及其受体(AGE-RAGE)等信号通路。结论 栀子豉汤可通过多成分、多靶点和多通路发挥治疗抑郁、焦虑和失眠的作用,为深入研究栀子豉汤的药效物质基础和药理作用提供理论依据。

Objective To explore the mechanism of Zhizichi Decoction in treatment of depression, anxiety and insomnia based on network pharmacology.Methods The main active ingredients of Zhizichi Decoction were screened. The target points corresponding to the components were obtained through PharmMapper and CTD. Intersection of component targets and depression, anxiety, and insomnia disease targets were obtained in TTD, OMIM, DrugBank, CTD, Gene-Cards, and DisGeNET databases, respectively. The intersection targets were imported into the String online website to construct a protein interaction network, and Cytoscape software was used for visual analysis, and the key targets were screened out according to the degree value. GO biological analysis and KEGG pathway enrichment analysis of the intersection target through the Matescape database. Cytoscape was used to construct a “componenttarget-pathway” network, and the core active ingredients were screened out according to the degree value.Results A total of 19 active ingredients were screened. The core active ingredients were daidzein, genistein, geniposide, rutin, isochlorogenic acid A, etc. The intersection of depression, anxiety, and insomnia components and disease targets respectively were 77, 91, and 111. KEGG pathway enrichment analysis results showed that the treatment of depression, anxiety, and insomnia by Zhizichi Decoction mainly involved estrogen, mitogen-activated protein kinase, PI3K-Akt, FOXO, neuroactive ligand-receptor interaction, IL-17, dopamine synapses, AGE-RAGE and other signaling pathways in diabetic complications.Conclusion Zhizichi Decoction plays a role in treatment of depression, anxiety and insomnia through multi-component, multi-target and multi-channel, which provides a theory for in-depth study of the pharmacological basis and pharmacological effects of Zhizichi Decoction.

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国家中药材产业技术体系专项(CARS-21);国家中医药管理局全国中药资源普查项目(GZY-KJS-2018-004);2018年中医药公共卫生服务补助专项“全国中药资源普查项目”(财社[2018]43号)