基于网络药理学探讨柴胡治疗卒中后抑郁的作用机制

To explore the mechanism of Radix Bupleuri in the treatment of post-stroke depression based on network pharmacology

目的基于网络药理学探讨柴胡治疗卒中后抑郁(PSD)的潜在靶点及作用机制。方法采用中药系统药理学数据库与分析平台(TCMSP)检索柴胡的有效成分及对应靶点,采用在线人类孟德尔遗传(OMIM)、疗效药靶(TTD)、Drugbank、Genecards数据库检索PSD的疾病靶点,二者靶点取交集后获得柴胡治疗PSD的潜在作用靶点;采用Cytoscape 3.7.1软件绘制中药-成分-疾病-靶点调控网络图;运用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络并分析其核心靶点;采用DAVID数据库对潜在靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)信号通路分析。结果柴胡治疗PSD的核心成分为异鼠李素、曲克芦丁、豆甾醇等,潜在靶点为蛋白激酶B(AKT1)、白细胞介素-6(IL-6)、内皮型一氧化氮合酶(NOS3)、肿瘤坏死因子(TNF)等,柴胡活性成分可以参与RNA聚合酶II启动子对转录的正调控、细胞间信号传递、对药物的反应、对凋亡过程的负调控、老化等生物过程,涉及的信号通路包括神经活性配体-受体相互作用、钙信号通路、癌症通路、磷脂酰肌醇-3激酶蛋白激酶B(PI3K-Akt)信号通路、环磷酸鸟苷酸依赖的蛋白激酶(cGMP-PKG)信号通路等。结论柴胡可能通过异鼠李素、曲克芦丁、豆甾醇等活性成分作用于AKT1、IL-6、NOS3等靶点,从而影响内分泌、炎症、免疫、代谢等相关通路来发挥治疗PSD的作用。

Objective To explore the potential target and mechanism of Radix Bupleuri in the treatment of post-stroke depression(PSD)based on network pharmacology.Methods The active components and corresponding targets of Radix Bupleuri were searched by TCMSP,and the disease targets of PSD were searched by OMIM,TTD,Drugbank and Genecards.The potential targets of Radix Bupleuri for the treatment of PSD were obtained by intersection of the two.Cytoscape 3.7.1 software was used to draw the regulatory network diagram of Chinese medicine-component-disease-target.The STRING database was used to construct the protein-protein interaction(PPI)network graph and analyze its core targets.DAVID database was used to perform Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for potential targets.Results The core components of Radix Bupleuri for the treatment of PSD were isorhamnetin,troxerutin,stigmasterol,etc.The potential targets were protein kinase B(AKT1),interleukin-6(IL-6),endothelial nitric oxide synthetase(NOS3),tumor necrosis factor(TNF),etc.The active ingredients of Radix Bupleuri can participate in the positive regulation of RNA polymeraseII promoter on transcription,intercellular signaling,response to drugs,negative regulation of apoptosis,aging and other biological processes.The signaling pathways involved include neural active ligandreceptor interaction,calcium signaling pathway,cancer pathway,phosphatidylinositol-3 kinase-protein kinase B(PI3K-Akt)signaling pathway,cyclic phosphoguanylate dependent protein kinase(cGMP-PKG)signaling pathway,etc.Conclusion Radix Bupleuri may act on AKT1,IL-6,NOS3 and other targets through isorhamnetin,troxerutin,stigosterol and other active components,thereby affecting endocrine,inflammatory,immune,metabolic and other related pathways to play a role in the treatment of PSD.