Na Zhu, Zi-Jun Sha, Jian-Wu H E, Cai-Feng L I, Feng-Rong Zhang, Jun-Qi Wang, Xiu-Lan Huang, Zhi-Yong L I
School of Pharmacy, Minzu University of China Beijing 100081, China.
National Joint Engineering Laboratory for Eucommia Utilization, Jishou University Jishou 416000, China.
Zhongguo Zhong Yao Za Zhi. 2020 Nov;45(22):5393-5402. doi: 10.19540/j.cnki.cjcmm.20200810.401.
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.
本研究旨在基于网络药理学和分子对接探索钩藤-杜仲降低血压的最佳适应证及作用机制。通过中药系统药理学数据库与分析平台（TCMSP数据库）收集并筛选化学成分。利用瑞士靶点预测平台预测药物相关靶点。使用在线孟德尔人类遗传数据库（OMIM）、中医整合药理学平台（TCMIP）和基因卡片数据库（GeneCards数据库）收集高血压相关基因，并取交集以获得钩藤-杜仲抗高血压治疗的潜在靶点。运用FunRich软件对降低血压潜在靶点的临床表型和表达部位进行富集，以分析和预测钩藤-杜仲的最佳适应证。利用STRING数据库进行京都基因与基因组百科全书（KEGG）通路富集分析，并使用Cytoscape 3.7.2构建“成分-靶点-通路”网络。分析并获取网络中的关键靶点及其相应成分，然后应用分子对接进行初步验证。分别收集了钩藤的20种潜在活性成分和杜仲的24种潜在活性成分，获得了钩藤-杜仲的92个抗高血压潜在靶点。根据FunRich富集结果，钩藤-杜仲的最佳适应证为妊娠高血压，涉及钙信号通路、缺氧诱导因子-1（HIF-1）信号通路、神经活性配体受体相互作用、肾素血管紧张、血管内皮生长因子（VEGF）信号通路等。此外，蛋白激酶B1（AKT1）、一氧化氮合酶2（NOS2）、β2肾上腺素能受体（ADRB2）、凝血因子Ⅱ（F2）、一氧化氮合酶3（NOS3）、钠通道蛋白5型α亚基（SCN5A）、5-羟色胺受体2A（HTR2A）和Janus激酶2（JAK2）被认为是网络中的关键靶点。分子对接结果表明，筛选出的潜在活性成分与关键靶点具有较高的结合活性。本研究初步揭示，钩藤-杜仲在镇静、抗高血压、抗炎、抗氧化、改善血管内皮功能等方面可能对妊娠高血压具有治疗作用。
