基于网络药理学探讨钩藤-桑寄生治疗原发性高血压的作用机制

Mechanism of Uncaria and Mulberry Parasitism for the Treatment of Essential Hypertension Based on Network Pharmacology

目的:基于网络药理学探讨钩藤-桑寄生治疗原发性高血压的潜在作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)检索并筛选出钩藤、桑寄生药对的药物活性成分及作用靶点。利用基因名片数据库(GeneCards)及DisGeNET数据库筛选原发性高血压的疾病靶点。利用韦恩平台(Venny)取活性成分作用靶点和疾病靶点交集,得到共同靶点。通过Cytoscape 3.9.1软件构建“药物-活性成分-靶点-疾病”网络。通过STRING数据库构建蛋白质相互作用(PPI)网络;利用Cytoscape CentisCape 2.2插件提取核心靶点进行分析,并构建“有效成分-核心靶点”网络图。利用DAVID数据库对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,并将富集结果可视化。结果:共筛选出钩藤-桑寄生的活性成分32个,作用于原发性高血压的主要靶点有丝氨酸/苏氨酸蛋白激酶B1(AKT1)、白细胞介素(IL)-6、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)等;主要集中于晚期糖基化终末产物(AGE)/糖基化终末产物受体(RAGE)信号通路、脂质与动脉粥样硬化通路、流体剪切应力和动脉粥样硬化通路、TNF信号通路、IL-17信号通路等。结论:钩藤-桑寄生药对可通过调节AKT1、IL-6、TNF、VEGFA等核心靶点调控AGE/RAGE、脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化、TNF、IL-17等多条信号通路,发挥治疗原发性高血压的作用。

Objective:To explore the potential mechanism of action of uncaria and mulberry parasitism for treating essential hypertension based on network pharmacology.Methods:Traditional Chinese medicine(TCM)system pharmacological database(TCMSP)was used to retrieve and screen the active drug components and targets of uncaria and mulberry parasitism.GeneCards and DisGeNET databases were used to search for disease targets of essential hypertension.The intersection of active ingredient components and disease targets were selected by Vennny platform.The“drug-active ingredient-target-disease”network diagram was constructed using Cytoscape 3.9.1 software.The protein interaction(PPI)network was constructed through the STRING online platform.Cytoscape CentisCape 2.2 plug-in was used to extract core targets for analysis and then constructed the“active ingredient-core target”network diagram.The DAVID database was used to perform Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of core targets,and the enrichment results were visualized.Results:A total of 32 active ingredients of uncaria and mulberry parasitism were screened,and the main targets of essential hypertension were serine/threonine protein kinase B1(AKT1),interleukin(IL)-6,tumor necrosis factor(TNF)and vascular endothelial growth factor A(VEGFA),which mainly focused on advanced glycation end product(AGE)/receptor for advanced glycation end products(RAGE)signaling pathway,lipid and atherosclerosis pathway,fluid shear stress and atherosclerosis pathway,TNF signaling pathway,IL-17 signaling pathway,etc.Conclusion:Uncaria and mulberry parasitism can regulate AGE/RAGE,lipid and atherosclerosis,fluid shear stress,atherosclerosis,TNF,IL-17,and other signaling pathway by regulating AKT1,IL-6,TNF VEGFA and other core targets,and play some role in the treatment of essential hypertension.