基于网络药理学的干姜治疗非酒精性脂肪性肝病的分子机制研究

A study on the molecular mechanism of rhizoma zingiberis in treating nonalcoholic fatty liver disease based on network pharmacology

目的:基于网络药理学方法分析干姜治疗非酒精性脂肪性肝病(Non-alcoholic Fatty Liver Disease,NAFLD)的药理机制,为新药研发及下一步的试验指导方向。方法:通过中药系统药理学数据库与分析平台数据库获取干姜主要化学成分,根据药物代谢动力学筛选中药活性组分;运用GeneCards、OMIM、TTD数据库获取NAFLD的主要靶点,通过String平台进行蛋白质-蛋白质相互作用分析,构建蛋白质-蛋白质相互作用网络并挖掘潜在的蛋白质功能模块。采用Metascape平台分析“干姜-成分-靶点”及其参与的生物过程及通路,而后采用Cytoscape 3.7.1软件构建“干姜-NAFLD靶点-通路”网络。结果:干姜治疗NAFLD的核心活性成分为6-姜辣素、β-谷甾醇、(10)-姜辣素等,核心靶点有RELA癌基因(RELA Proto-Oncogene,RELA)蛋白、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、肿瘤蛋白P53(Tumor Protein P53,TP53)等。干姜治疗NAFLD的生物学通路主要富集于神经元凋亡过程的调控、神经元死亡的正调节、神经元死亡的调节、神经元凋亡过程等,其功能主要为调节细胞内蛋白质同源二聚化活动等。结论:本研究揭示了干姜治疗NAFLD潜在的靶点及通路,为进一步的分子验证及实验设计提供了理论基础。

Objective:To analyze the pharmacological mechanism of rhizoma zingiberis on NAFLD based on network pharmacology,and to provide guidance for new medicine research and development and further trial.Methods:The main chemical constituents of rhizoma zingiberis were obtained by TCMSP database.The active components of Chinese materia medica were screened according to pharmacokinetics.GeneCards,OMIM,and TTD databases were used to capture NAFLD’s main targets.An analysis of protein-protein interaction was analyzed by String platform.A protein-protein interaction network was constructed,and potential protein functional modules were explored.Metascape platform was used to analyze“rhizoma zingiberis-component-target”and its biological processes and pathways.Then Cytoscape 3.7.1 software was used to construct“rhizoma zingiberis-NAFLD target-pathway”network.Results:The core active ingredients of rhizoma zingiberis in treating NAFLD are 6-gingerol,beta-sitosterol,(10)-gingerol,etc.The core targets include RELA protein,TNF,TP53 and so on.The biological pathways of rhizoma zingiberis on NAFLD are mainly enriched in regulation of neuronal apoptosis,positive regulation of neuron death,regulation of neuronal death,process of neuronal apoptosis and so on.Its function is mainly to regulate the homologous dimerization of proteins in cells and so on.Conclusion:This study reveals the targets and pathways of rhizoma zingiberis on NAFLD,provides a theoretical basis for further molecular verification and experimental design.