摘要
目的:通过网络药理学方法探讨知柏地黄丸治疗高血压的潜在靶点及信号通路。方法:通过TCMSP、Swiss Target Prediction、DrugBank数据库,对中药知柏地黄丸中8味药物的主要有效成分进行检索,并预测其靶点。结合OMIM、GeneCards、DisGeNET、TTD数据库搜索高血压的相关靶点,将二者取交集。运用STRING数据库得到知柏地黄丸作用于高血压的PPI网络,然后使用Cytoscape对PPI网络进行拓扑分析得到关键靶点。最后基于R语言、Metascape软件及DAVID数据库进行基因本体论(gene ontology,GO)功能富集和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集。结果:共得到IL-6、VEGFA、PTGS2、CASP3、JUN等30个知柏地黄丸与高血压的关键相互作用靶点。GO功能富集分析显示,知柏地黄丸治疗高血压与腺苷酸环化酶激活肾上腺素能受体信号通路、葡萄糖稳态、类固醇代谢过程等相关。KEGG通路富集发现知柏地黄丸治疗高血压关联神经活性配体-受体相互作用、含血清素的神经突触、卵巢类固醇生成,缺氧诱导因子1(hypoxia-inducible factor-1,HIF-1)信号通路等多条通路。结论:知柏地黄丸降压的潜在生物学作用机制是通过调控神经活性配体-受体相互作用、含血清素的神经突触,HIF-1信号通路等发挥治疗作用,反映了知柏地黄丸多成分、多靶点,多环节协调治疗高血压的特点。
Objective:To discuss the potential targets and signaling pathways of Zhibai Dihuang pills in the treatment of hypertension through network pharmacology.Methods:The main active ingredients of eight herbs contained in Chinese patent drug Zhibai Dihuang pills were searched from TCMSP,Swiss Target Prediction and DrugBank,and the prediction of the targets were conducted.Meanwhile,hypertension-related targets were retrieved from OMIM,GeneCards,DisGeNET and TTD databases,to obtain the intersection from both.STRING database was applied to gain PPI network after treating hypertension with the medicine,the topology analysis of PPI network was carried out using Cytoscape so as to gain the key targets.Consequently,GO and KEGG were performed based on R language,Metascape software and DAVID databases.Results:There were 30 key interaction targets between Zhibai Dihuang pills and hypertension,covering IL-6,VEGFA,and PTGS2,CASP3 and JUN.GO functional enrichment analysis displayed that the treatment of hypertension with Zhibai Dihuang pills was related to adenylate cyclase-activating adrenergic receptor signaling pathway,glucose homeostasis and steroid metabolism.KEGG pathway enrichment indicated that Zhibai Dihuang pills in the treatment of hypertension was associated with many pathways such as neuroactive ligand-receptor interaction,serotonin-containing synapses,ovarian steroid generation and HIF-1 signaling pathway.Conclusion:The potential biological mechanism of Zhibai Dihuang pills in lowering blood pressure could exert therapeutic effects by regulating neuroactive ligand-receptor interaction,serotonin-containing synapses,ovarian steroid generation and HIF-1 signaling pathway,reflecting the characteristics of multi-component,multi-target and multi-link coordinated treatment of hypertension by Zhibai Dihuang Pills.
作者
蒋欣琪
卢涛
于国华
董易杭
张金东
毛伯䶮
文雅倩
张晓晴
JIANG Xinqi;LU Tao;YU Guohua;DONG Yihang;ZHANG Jindong;MAO Boyan;WEN Yaqian;ZHANG Xiaoqing(Beijing University of Chinese Medicine,Beijing 100029,China;Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Tianjin Research Institute for Advanced Equipment,Tsinghua University,Tianjin 300308,China)
出处
《西部中医药》
2025年第5期38-46,共9页
Western Journal of Traditional Chinese Medicine
基金
国家重点研发计划项目(2017YFC1703306)。
关键词
高血压
知柏地黄丸
网络药理学
潜在靶点
功能富集
通路富集
hypertension
Zhibai Dihuang pills
network pharmacology
potential targets
functional enrichment
pathway enrichment