基于网络药理学和分子对接探讨王行宽教授治疗高血压核心处方平肝煎的作用机制  

Mechanism of Professor Wang Xingkuan′s Core Prescription Pinggan Decoction in the Treatment of Hypertension Based on Network Pharmacology and Molecular Docking

作　　者：王子焱 范金茹[1] 范建民[1] 周婕 李苏[1] WANG Ziyan;FAN Jinru;FAN Jianmin;ZHOU Jie;LI Su(The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China)

机构地区：[1]湖南中医药大学第一附属医院,长沙410007

出　　处：《中西医结合心脑血管病杂志》2023年第22期4049-4056,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家中医药管理局·湖南省中医药管理局“王行宽全国名中医传承工作室”建设项目,编号:国中医药办人教函[2018]119号;湖南省教育厅一般项目(No.20C1437);重大疑难疾病慢性心力衰竭中西医临床协作试点项目,编号:国中医药办医政发[2018]3号。

摘　　要：目的:运用网络药理学研究王行宽教授治疗高血压核心处方平肝煎的作用机制,并通过分子对接技术进行初步验证。方法:通过中药系统药理学数据库与分析平台(TCMSP)数据库和本草组鉴数据库(HERB)筛选平肝煎的活性化合物并预测其作用靶点,运用Cytoscape 3.8.2软件进行网络拓扑学分析;以“hypertension”为关键词在基因名片数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、药物数据库(DrugBank)搜索高血压疾病相关靶点,并与平肝煎化合物作用靶点取交集,通过生物分子功能注释系统(STRING)数据库构建蛋白质-蛋白质相互作用(PPI)网络图;将关键靶点导入R软件和采用clusterProfiler进行富集分析,并使用AutoDock程序及PyMol进行分子对接。结果:平肝煎筛选得到有效成分30个、相关作用靶点387个,与高血压的共同靶点279个,经STRING平台和Cytoscape 3.8.2拓扑分析度值(Degree)靠前的靶标为蛋白激酶B1(AKT1)、肿瘤蛋白P53(TP53)、肿瘤坏死因子(TNF)、白细胞介素6(IL-6)、Jun原癌基因(JUN)。基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析提示中药复方可能通过调控细胞核转录因子、参与脂多糖等反应来干预治疗高血压。分子对接结果显示,槲皮素与TNF、AKT1的结合活性较好。结论:平肝煎中的大黄素、槲皮素、山柰酚可作用于AKT1、TP53、TNF、IL-6、JUN等靶点,通过抗炎、抗氧化应激、改善血管内皮功能、调节机体免疫方面发挥降血压之效。Objective:To study the mechanism and pathway of Pinggan Decoction of Professor Wang Xingkuan for treating hypertension,by using network pharmacology,and preliminarily verify it by molecular docking technology.Methods:The active compounds of Pinggan Decoction were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and HERB and their target sites were predicted.The network topology was analyzed by the software of Cytoscape 3.8.2.Using"hypertension"as the key word,The targets related to hypertension were searched in GeneCards,OMIM,and DrugBank,and the targets of Pinggan decoction were intersected.The protein protein interaction(PPI)network diagram was constructed through STRING platform.Key targets were imported into R software,enriched and analyzed with clusterProfiler,and molecular docking was performed with Autodock program and Pymol.Results:Pinggan Decoction screened 30 active ingredients,387 related action targets,and 279 common targets with hypertension.The top targets through the STRING platform and Cytoscape 3.8.2 topological analysis were protein kinase B1(AKT1),tumor protein p53(TP53),tumor necrosis factor(TNF),interleukin-6(IL-6),and JUN.The analysis of genetic ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis suggested that Chinese herbal compound might intervene in the treatment of hypertension by regulating nuclear transcription factors and participating in lipopolysaccharide reactions.The results of molecular docking showed that the binding activity of quercetin with TNF and AKT1 was better.Conclusion:Emodin,quercetin,and kaempferol in Pinggan Decoction can act on AKT1,TP53,TNF,IL-6,JUN,and other targets,and play a role in lowering blood pressure through anti-inflammatory,anti oxidative stress,improving vascular endothelial function,and regulating body immunity.

关 键 词：高血压 平肝煎 网络药理学 分子对接 作用靶点 信号通路 

分 类 号：R285[医药卫生—中药学]