基于网络药理学的六味地黄丸治疗高血压作用机制探讨

目的:基于网络药理学探索六味地黄丸治疗高血压的分子机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集六味地黄丸的有效化合物,在PharmMapper数据库中预测化合物可能的靶点,与GeneCards数据库中高血压相关靶点相映射,获得六味地黄丸调节高血压的可能作用靶点;对这些靶点进行蛋白质-蛋白质相互作用(PPI)网络的构建、基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析,以揭示六味地黄丸治疗高血压可能的作用机制;运用AutoDock进行分子对接验证。结果:共筛选出六味地黄丸中的69个化合物及269个作用靶点,其中作用于高血压的相关靶点有14个;PPI网络显示,血清白蛋白(ALB)、一氧化氮合酶3 (NOS3)、表皮生长因子受体(EGFR)、肾素(REN)是4个联系最多的靶点,涉及对胆固醇的反应、血小板活化的负调节等生物过程,作用机制与调控黏附分子表达、破骨细胞分化、FoxO信号通路、肾素-血管紧张素系统等生物学通路有关。结论:六味地黄丸治疗高血压的主要成分有茯苓酸、泽泻醇、芍药苷、谷甾醇、豆甾醇等,ALB、NOS3、EGFR、REN是其主要作用靶点。

Mechanism of Liuwei Dihuang Pill in Treatment of Hypertension Based on Network Pharmacology

Objective To determine the molecular mechanism of Liuwei Dihuang Pill in the treatment of hypertension.Methods The active compounds of Liuwei Dihuang Pill were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the possible targets were predicted in PharmMapper, which were mapped with hypertension-related targets in GeneCards to obtain the possible targets of Liuwei Dihuang Pill in regulating hypertension. These targets were subjected to protein-protein interaction (PPI) network construction, gene ontology (GO) enrichment analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for revealing the possible mechanism of Liuwei Dihuang Pill against hypertension. The molecular docking verification was then carried out using AutoDock.Results A total of 69 compounds and 269 targets were screened out for Liuwei Dihuang Pill, of which 14 acted on hypertension-related targets. As demonstrated by the PPI network, serum albumin (ALB), nitric oxide synthase 3 (NOS3), epidermal growth factor receptor (EGFR), and renin (REN) were the main targets, with such biological processes as cholesterol response and negative regulation of platelet activation involved. The action mechanism was mainly related to the regulation of adhesion molecule expression, osteoclast differentiation, FoxO signaling pathway, and renin-angiotensin system.Conclusion The main components responsible for the treatment of hypertension in Liuwei Dihuang Pill are pachymic acid, alisol, paeoniflorin, sitosterol, and stigmasterol, with ALB, NOS3, EGFR, and REN being the main targets.