枸杞子-菊花药对治疗高血压作用机制的网络药理学研究

Mechanism of Gouqizi-Juhua Herb Pair in Treatment of Hypertension Based on Network Pharmacology

目的采用网络药理学枸杞子-菊花药对治疗高血压的作用机制。方法利用TCMSP筛选枸杞子-菊花的主要有效成分、治疗潜在靶点,通过GeneCards检索高血压疾病基因,运用Venny 2.1软件筛选枸杞子-菊花与高血压的共同靶点,然后Cytoscape 3.7.2软件进行中药-化学成分-共同靶点可视化网络,使用STRING 11.0在线数据库,对共同靶点间蛋白相互作用进行分析及筛选关键靶点,运用Metascape在线数据库对共同靶点进行GO和KEGG通路分析。结果枸杞子-菊花共120个靶点,高血压疾病靶点筛选后1 003个,其中有61个为枸杞子-菊花治疗高血压的共同靶点,Cytoscape 3.7.2软件网络视图中度值较高的化合物是檞皮素、山柰酚、木犀草素,枸杞子-菊花治疗高血压的关键靶点为依次为JUN、MAPK1、MAPK3、MAPK8、TP53、ESR1、NR3C1、IL6、TNF、IL2。GO富集分析显著的通路有细胞外刺激反应、循环系统中的血管进程、营养水平的反应、毒性物质的反应、血液循环系统等;KEGG富集分析显著的通路包括糖尿病并发症中AGE-RAGE信号通路、流体剪切力与动脉粥样硬化、IL-17信号通路、肿瘤坏死因子信号转导通路等。结论枸杞子-菊花治疗高血压是通过多成分、多靶点、多通路的协同作用,为深入探讨作用机制奠定了基础。

OBJECTIVE To explore the mechanism of Gouqizi-Juhua in treatment of hypertension by network pharmacology. METHODS Active components and therapeutic potential targets of Gouqizi-Juhua were screened by TCMSP database. Hypertension genes were searched by GeneGards database. Using Venny2.1 to find out the common targets, then common targets were used to constructe the visual network map of Chinese medicine-chemical constituents-common targets through Cytoscape3.7.2 software and construct the protein interaction network map by STRING 11.0 database for analysis and screening of key targets. Finally, GO and KEGG enrichment analysis of common targets were carried out by Metascape database. RESULTS After screening, a total of 120 related targets were obtained, 1 003 targets related to hypertension were screened, and 61 among them were the common targets of Gouqizi-Juhua in the treatment of hypertension. The Cytoscape 3.7.2 software network view analysis showed that ingredients with higher degrees included quercetin, kaempferol, luteolin. Key targets involved JUN、MAPK1、MAPK3、MAPK8、TP53、ESR1、NR3 C1、IL6、TNF and IL2. GO enrichment analysis revealed that common targets were associated with response to extracellular stimulus, vascular process in circulatory system, response to nutrient levels, response to toxic substance, blood circulation and so on. Signaling pathways in KEGG enrichment analysis revealed that AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, IL-17 signaling pathway, TNF signaling pathway and so on. CONCLUSION Hypertension is treated by Gouqizi-Juhua through the synergistic effect of multi-components, multi-targets and multi-pathways, wich lays a good foundation for further study on the mechanism of action.