大明胶囊治疗高脂血症的网络药理学分析及分子对接验证研究

Network pharmacological analysis and molecular docking validation study of Daming Capsule in the treatment of hyperlipidemia

目的基于网络药理学方法分析大明胶囊治疗高脂血症的活性成分及其作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索并筛选大明胶囊的主要化学成分及靶点,通过GeneCards、DisGeNET及DrugBank数据库挖掘高脂血症靶点,取交集得到大明胶囊治疗高脂血症的靶点。将上述靶点导入STRING数据库,构建PPI网络并挖掘网络中潜在的蛋白质功能模块;利用R语言ClusterProfiler GO.R插件对交集靶点进行GO和KEGG通路富集分析。利用Cytoscape 3.7.2软件构建“活性成分-疾病靶点-通路”网络图,并对网络进行拓扑学参数分析筛选活性成分及关键靶点。利用AutoDock Vina软件进行分子对接验证。结果共筛选得到大明胶囊活性成分70个,作用靶点196个,高脂血症相关靶点541个。大明胶囊治疗高脂血症的重点活性成分为山柰酚,核心靶点为HSP90AA1、NCOA2、AKT1、ADRB2、RXRA、TNF、NCOA1、PPARG、MAPK1、IL-6、IL-1β、ESR1。分子对接结果显示,山柰酚与核心靶点具有良好的结合能力。大明胶囊治疗高脂血症主要通过脂质和动脉粥样硬化信号通路、糖尿病并发症AGE-RAGE信号通路等,其功能主要为调节细胞内受体配体活动等过程。结论本研究初步阐明了大明胶囊治疗高脂血症多成分、多靶点、多通路的作用机制,为大明胶囊治疗高脂血症的中药药理学研究提供理论基础和参考依据。

Objective To analyze the active components and mechanism of action of Daming Capsule in treating hyperlipidemia based on network pharmacological method.Methods The main chemical components and targets of Daming Capsule were retrieved and screened from TCMSP database.The hyperlipidemia targets were retrieved from GeneCards,DisGeNET and DrugBank databases,and the target of Daming Capsule for hyperlipidemia was obtained by taking the intersection.The above targets were imported into STRING database,the PPI network was built and potential protein functional modules in the network were mined.The R language ClusterProfiler GO.R plug-in was utilized to conduct GO and KEGG pathway enrichment analysis for intersection targets.The network map of"active component-disease target-pathway"was constructed by using the software Cytoscape 3.7.2,and the topological parameters of the network were analyzed to screen the active components and key targets.AutoDock Vina software was used for molecular docking validation.Results A total of 70 active components,196 action targets and 541 hyperlipidemia related targets of Daming Capsule were screened.The key active component of Daming capsule in treating hyperlipidemia was kaempferol,and the core targets were HSP90AA1,NCOA2,AKT1,ADRB2,RXRA,TNF,NCOA1,PPARG,MAPK1,IL-6,IL-1βand ESR1.The results of molecular docking showed that kaempferol had good binding ability to the core targets.Daming capsule for hyperlipidemia mainly utilized lipid and atherosclerosis signaling pathway and AGE-RAGE signaling pathway in diabetes complications,and its function was mainly to regulate the activities of intracellular receptors and ligands and other processes.Conclusion This study preliminarily clarifies the mechanism of action of Daming Capsule in treating hyperlipidemia with multiple components,multiple targets and multiple pathways,and provides theoretical basis and reference for the pharmacological study of traditional Chinese medicine in the treatment of hyperlipidemia with Daming Capsule.