大柴胡汤治疗高血压病潜在机制的网络药理学研究

Network Pharmacology Study on the Potential Mechanism of Dachaihu Decoction in the Treatment of Hypertension

目的:基于网络药理学的研究方法,对大柴胡汤治疗高血压病的作用机制进行预测分析。方法:从中药系统药理学分析平台,根据口服利用度≥30%和类药性≥0.18分析,对大柴胡汤有效活性成分进行筛选;采用Swiss Target Prediction数据库检索成分相对应的靶点,构建"中药-化合物-靶点"网络图;利用OMIM、DisGeNET、PharmGKB等不同数据库检索高血压病相关靶点;进一步对药物和疾病靶点进行相互映射,得到大柴胡汤治疗高血压病的直接作用靶点;运用STRING构建药物-疾病相互作用网络图,进一步通过Cytoscape3.6.1软件中CytoNCA插件筛选出关键靶点;采用ClueGO插件、Funrich软件和生物学信息注释库对直接作用靶点进行GO分析和KEGG通路分析。结果:大柴胡汤筛选得到135个活性成分,涉及170个潜在靶点;1169个高血压病靶点;药物与疾病直接作用靶点84个,涉及55条相关通路。大柴胡汤可能通过白细胞介素-6(interleukin-6 IL-6)、IL-1β、肿瘤坏死因子(tumor necrosis factor,TNF)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、一氧化氮氧合酶(nitric oxide synthase,NOS3)等关键靶点发挥降血压作用;参与TNF信号通路、钙信号通路、VEGF信号通路、神经活性配体-受体相互作用通路等各个途径发挥对血压的调控作用。结论:大柴胡汤治疗高血压病的作用机制涉及高血压病炎症反应、血管内皮功能、钙离子通道转运、神经活性受体诸多方面,为深入阐明其作用机制开辟了新途径。

Objective:To predict and analyze the mechanism of Dachaihu Decoction in the treatment of hypertension based on the research method of network pharmacology.Methods:According to the oral utilization(OB≥30%)and medicine analogues analysis(DL≥0.18),the active components of Dachaihu Decoction were screened from the platform of systematic pharmacology of Chinese medicine.Swiss Target Prediction database was used to search the target points corresponding to the components,and the network diagram of"Chinese materia medica-compound-target"was constructed.OMIM,DisGeNET,PharmGKB and other databases were used to search hypertension related targets.The direct target of Dachaihu Decoction in the treatment of hypertension was obtained by further mapping the meidicine and disease targets.The medicine-disease interaction network was constructed by using STRING,and the key targets were screened by using the CytoNC plug-in in Cytoscape3.6.1 software.ClueGO plug-in,Funrich software and biological information annotation library were used to analyze the GO and KEGG pathway of direct targets.Results:135 active components were screened from Dachaihu Decoction,involving 170 potential targets;1169 targets for hypertension;84 targets for direct interaction between medicine and diseases,involving 55 related pathways.Dachaihu Decoction may exert antihypertensive effect through key targets such as interleukin-6(IL-6),IL-1β,tumor necrosis factor(TNF),vascular endothelial growth factor(VEGF)and nitric oxide synthase(NOS3).It is involved in TNF signaling pathway,calcium signaling pathway,VEGF signaling pathway,and neuroactive ligand receptor interaction pathway to regulate blood pressure.Conclusion:135 active components were screened from Dachaihu decoction,involving 170 potential targets;1169 targets for hypertension;84 targets for direct interaction between medicine and diseases,involving 55 related pathways.