基于网络药理学及分子对接技术探究地骨皮–葛根治疗高血压的作用机制

Study on the Mechanism of Lycii Cortex-Puerariae lobatae Radix Herb Pair in the Treatment of Hypertension Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：运用网络药理学及分子对接技术探究地骨皮–葛根药对治疗高血压的作用机制。方法：利用TCMSP数据库及Uniprot数据库筛选地骨皮–葛根的有效成分和作用靶点，通过GeneCards、OMIM、TTD及DrugBank疾病数据库搜索高血压相关靶点。运用Venny数据库构建地骨皮–葛根药对和高血压靶点韦恩图，获得交集靶点；将获得的交集靶点上传至STRING数据库进行蛋白质–蛋白质相互作用(PPI)网络预测。利用Metascape数据库进行GO和KEGG富集分析。应用Cytoscape3.9.0软件制作“药物–成分–靶点”、蛋白质–蛋白质相互作用(PPI)、“成分–靶点–通路”网络图。最后采用AutoDockTools软件对主要活性成分和核心靶点进行分子对接验证。结果：筛选出地骨皮–葛根有效化合物21个，对应作用靶点169个，药物与疾病共同作用靶点98个；蛋白互作网络中核心基因为STAT3、AKT1、CAV1、ESR1、TP53；KEGG分析显示主要通路有神经活性配体–受体相互作用、脂质与动脉粥样硬化、cGMP-PKG信号通路等。分子对接结果显示，地骨皮–葛根药对的主要活性成分与关键靶点具有较强的结合能力。结论：地骨皮–葛根药对治疗高血压具有多成分、多靶点、多通路的特点，为该药对的临床应用和高血压的治疗提供了基础。

Abstract: Objective: To study the mechanism of lycii cortex-Puerariae lobatae radix herb pair in the treatment of hypertension based on network pharmacology and molecular docking technique. Methods: The effective components and targets of lycii cortex-Puerariae lobatae radix were screened by TCMSP database and Uniprot database, and the hypertension-related targets were searched by GeneCards, OMIM, TTD and DrugBank disease database. The Venn diagram of lycii cortex-Puerariae lobatae radix herb pair and hypertension target was constructed by Venny database, and the intersection target was obtained, and the intersection target was uploaded to STRING database for protein-protein interaction (PPI) network prediction. GO and KEGG enrichment analysis was carried out by using Metascape database. The network diagrams of “drug-component-target”, protein-protein interaction (PPI) and “component-target-pathway” were made by Cytoscape3.9.0 software. Finally, the AutoDockTools software was used to verify the molecular docking of the main active components and core targets. Results: A total of 21 effective compounds and 169 corresponding targets were selected from the lycii cortex-Puerariae lobatae radix herb pair, of which 98 were common targets of drugs and diseases. The key genes are STAT3, AKT1, CAV1, ESR1 and TP53 in PPI; KEGG showed that the main pathways were neuroactive ligand-receptor interaction, lipid and atherosclerosis, cGMP-PKG signal pathway and so on. The results of molecular docking showed that the main active components and key targets of lycii cortex-Puerariae lobatae radix had strong binding ability. Conclusion: Lycii cortex-Puerariae lobatae radix has the characteristics of multi-component, multi-target and multi-pathway in the treatment of hypertension, which pro-vides a basis for its clinical application and the treatment of hypertension.