基于网络药理学和分子对接的钩藤-杜仲药对治疗妊娠高血压病的潜在作用价值发现与研究

Discovery and study on potential effect of herbal pair of Uncariae Ramulus cum Uncis-Eucommiae Cortex on pregnancy hypertension based on network pharmacology and molecular docking

采用网络药理学和分子对接的方法探讨钩藤-杜仲药对在降压方面的最优适应症及其作用机制。通过TCMSP数据库搜集化学成分并筛选得到潜在活性成分,Swiss Target Prediction平台预测药物相关靶点;OMIM,TCMIP和GeneCards数据库搜集高血压疾病相关基因,取交集获取钩藤-杜仲降压的潜在靶标;FunRich软件对降压潜在靶标进行临床表型和表达部位富集,分析预测钩藤-杜仲最优适应症;利用STRING数据库进行KEGG通路富集分析,Cytoscape 3.7.2软件构建"成分-靶点-通路"网络,分析获取网络中的关键靶点与其对应成分,并利用分子对接进行初步验证。分别搜集得到钩藤、杜仲潜在活性成分20个和24个,钩藤、杜仲降压潜在靶标92个;根据FunRich富集结果,钩藤-杜仲最优适应症为妊娠高血压病,作用通路涉及钙信号通路、HIF-1信号通路、神经活性配体-受体相互作用、肾素-血管紧张素系统、VEGF信号通路等;AKT1,NOS2,ADRB2,F2,NOS3,SCN5A,HTR2A,JAK2为网络中的关键靶点;分子对接结果显示,筛选出的潜在活性成分与关键靶点之间具有较高的结合活性。该研究初步揭示了钩藤-杜仲药对在治疗妊娠高血压病方面具有镇静、降压、抗炎、抗氧化、改善血管内皮功能等潜在功效。

This study aimed to explore the optimal indications and mechanism of Uncariae Ramulus cum Uncis(UR)-Eucommiae Cortex(EC) in lowering blood pressure based on network pharmacology and molecular docking. Chemical constituents were collected and screened by TCMSP database. Swiss Target Prediction platform was used to predict the related targets of the drug. OMIM, TCMIP and GeneCards databases were used to collect hypertension-related genes, and the intersections were taken to obtain potential targets for anti-hypertensive treatment of UR-EC. FunRich software was used to enrich the clinical phenotype and expression site of potential target of lowering blood pressure to analyze and predict the optimal indications of UR-EC. STRING database was used for KEGG pathway enrichment analysis, and Cytoscape 3.7.2 was used to construct the network of "composition-target-pathway". The key targets and their corresponding components in the network were analyzed and obtained, and then molecular docking was applied for preliminary verification. Twenty potential active components of UR and 24 potential active components of EC were respectively collected, and 92 anti-hypertensive potential targets of UR-EC were obtained. According to FunRich enrichment results, the optimal indication of UR-EC was pregnancy hypertension, which involved calcium signaling pathway, HIF-1 signaling pathway, neuroactive ligand receptor interaction, renin vascular tightening, VEGF signaling pathway, etc. In addition, AKT1, NOS2, ADRB2, F2, NOS3, SCN5 A, HTR2 A and JAK2 were considered as the key targets in the network. The molecular docking results showed that the screened potential active components had high binding activity with the key targets. This study preliminarily revealed that UR-EC may have therapeutic effects on pregnancy hypertension in terms of sedation, anti-hypertension, anti-inflammatory, anti-oxidation, improvement of vascular endothelial function and so on.