黄精四草汤治疗高血压病作用机制的网络药理学研究

Study of Mechanism of Huangjing Sicao Decoction(黄精四草汤)for Hypertension Based on Network Pharmacology

目的:基于网络药理学的方法,探讨黄精四草汤治疗高血压病的作用机制,为中医药防治高血压病提供新的策略。方法:从中药系统药理学分析平台(TCMSP)中查找与黄精四草汤5味中药相关的所有成分和作用靶点,结合口服生物利用度(OB≥30%)和类药性分析(DL≥0.18),筛选黄精四草汤的活性成分及作用靶点;运用Cytoscape3.6.1构建"中药-成分-靶点"网络图;利用TTD、OMIM、GAD等多个数据库检索高血压病疾病靶点,将两者相互映射后获取黄精四草汤治疗高血压病的作用靶点。运用HPRD构建直接作用靶点相互作用网络,结合Cytoscape3.6.1软件对网络可视化展示,使用Network Analyzer进行拓扑分析,筛选出关键基因。采用生物学信息注释库(DAVID)对靶点基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析。结果:从黄精四草汤中共筛选出活性成分31个,主要包括β-谷甾醇、木犀草素、黄芩素等;与高血压相关的关键靶点63个,包括白细胞介素-6(IL-6)、一氧化氮合成酶3(NOS3)、前列腺素内过氧化物合酶2(PTGS2)等。黄精四草汤治疗高血压病的生物过程主要涉及细胞信号转导、氧化还原反应等方面。黄精四草汤主要通过神经活性配体-受体相互作用通路、钙信号通路、肿瘤坏死因子信号通路、5-羟色胺能突触通路等发挥治疗高血压病的作用。结论:黄精四草汤治疗高血压病的潜在作用机制涉及多成分、多靶点、多通路,为进一步探讨黄精四草汤治疗高血压病的作用靶点及药效物质研究提供了理论依据。

Objective:To study the mechanism of Hungjing Sicao Decoction ( 黄精四草汤 ) (HSD) in the treatment of hypertension using network pharmacology,and to provide a new strategy for the treatment of hypertension in traditional Chinese medicine(TCM). Methods:The components and targets of the five medicinals in HSD were searched in the Traditional Chinese Medicine System Pharmacology Databased and Analysis Platform(TCMSP). With oral availability ≥30% and druglikeness ≥0.18,the active ingredients and targets of HSD were screened.Cytoscape 3.6.1 was applied to construct a network of "medicinals-components-targets". Databases like TTD,OMIM and GAD were searched for hypertension-related disease targets,and after mutual reflection,the targets of hypertension treated with HSD was obtained. HPRD was applied to construct a drug-disease interaction network,and combined with Cytoscape 3.6.1,the network was visualized and displayed. Network Analyzer was applied to perform topological analysis to screen the key genes. In the Database for Annotation Visualization and Integrated Discovery(DAVID), Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis for the target genes were analyzed. Results:A total of 31 active ingredients were screened from HSD,mainly including β-sitosterol,luteolin,baicalein,etc. There were 63 targets related to hypertension, including interleukin-6( IL-6), nitric oxide synthase 3( NOS3), prostaglandin endoperoxidase synthase 2(PTGS2),etc. The biological process of HSD in the treatment of hypertension mainly involved cell signal transduction and redox reaction and other aspects. HSD treated hypertension mainly through neural active ligand-receptor interaction pathway,calcium signal pathway,tumor necrosis factor signal pathway,serotonergic synaptic pathway,etc. Conclusion:The mechanism of HSD in the treatment of hypertension involves multiple components,multiple targets,and multiple pathways. This study will provide a theoretical basis for further research on the targets and medicinal substances of the HSD in the treatment of hypertension.