基于网络药理学探讨黄芪治疗代谢相关脂肪性肝病作用机制

Mechanism of Astragali Radix in treatment of metabolic associated fatty liver disease based on network pharmacology

目的使用网络药理学方法探讨黄芪治疗代谢相关脂肪性肝病(MAFLD)的作用机制。方法根据TCMSP数据库、GeneCards数据库和比较毒物基因组学数据库数据库,预测和筛选黄芪的活性成分和MAFLD的相关基因,得到黄芪治疗MAFLD的潜在靶点,使用Cytoscape 3.8.0软件和STRING数据库,构建黄芪活性成分与MAFLD相关靶点的成分-靶点网络,分析网络获得重要靶点,并利用Metascape数据库对其进行GO和KEGG通路富集分析。结果从黄芪中筛选得到叶酸、槲皮素、山柰酚、异鼠李素等20个活性成分,能够作用于91个MAFLD相关靶点,其中IL4、EGFR、MAPK8、TNF、HIF-1α等27个靶点是重要靶点,可能通过调控糖尿病并发症AGE-RAGE信号通路、白细胞介素-17信号通路、流体剪切应力与动脉粥样硬化等通路,参与调节MAFLD脂质代谢、氧化应激反应和炎症反应等多种生物过程。结论黄芪可以通过多靶点、多途径参与MAFLD的治疗。

Objective To investigate the mechanism of Astragali Radix in treatment of metabolic associated fatty liver disease(MAFLD)by means of network pharmacology.Methods According to TCMSP database,GeneCards database,and Comparative Toxicogenomics database,predict and screen the active ingredients of Astragali Radix and related genes of MAFLD,obtain the potential targets of Astragali Radix for treating MAFLD.Cytoscape 3.8.0 software and STRING database was used to construct a component-target network between active ingredients and potential targets.Analyze the network to obtain important targets,and use Metascape database to annotate important targets with gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Astragali Radix contains 20 active components such as quercetin,kaempferol,isorhamnetin and folic acid,which can act on 91 MAFLD targets.Among them,27 targets are key targets,such as IL4,EGFR,MAPK8,TNF and HIF-1α,which can regulate AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,fluid shear stress and atherosclerosis,involved lipid metabolism,oxidative stress and inflammatory response and other biological processes.Conclusion Astragali Radix play a role in treatment of MAFLD through multiple targets and pathways.