枸骨叶治疗非酒精性脂肪肝病生物学靶点网络药理学研究

Network pharmacology study on Ilex cornuta folium in the treatment of non-alcoholic fatty liver disease

目的通过网络药理学研究枸骨叶治疗非酒精性脂肪肝病(NAFLD)的生物学靶点和作用机制。方法通过本草组鉴(HERB)数据库、SwissADME和中医药系统药理学(TCMSP)数据库筛选枸骨叶的活性成分,通过TCMSP和Swiss Target Prediction和GeneCards数据库获得相关靶点,使用Cytospace和STRING绘制化合物-靶点-疾病和蛋白-蛋白互作网络(PPI)图,使用DAVID数据库进行基因功能分类体系(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果分离得到槲皮素、山柰酚、多梗白菜菊素高中心度化合物,血管内皮生长因子A(VEGFA)、白细胞介素-1β(IL-1β)和肿瘤坏死因子(TNF)等10个关键蛋白。富集分析显示,枸骨叶治疗NAFLD与TNF、IL-17和晚期糖基化产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路有关。分子对接显示关键化合物和关键靶点对接较好。结论枸骨叶通过调控TNF、IL-17、AGE-RAGE、CLR和TLR信号通路,治疗NAFLD。

Objective To investigate the biological targets and mechanism action of treatment of non-alcoholic fatty liver disease(NAFLD)effect of Ilex cornuta folium based on network pharmacology.Methods Through the HERB database,SwissADME,and Traditional Chinese Medicine Systems Pharmacology Platform(TCMSP)database,active ingredients of Ilex cornuta folium were screened.Relevant targets were obtained through TCMSP,Swiss Target Prediction,and GeneCards databases.Compound-target-disease and protein-protein interaction(PPI)networks were constructed using Cytospace and STRING.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed using the DAVID database.Results Separate and obtain high concentration compounds of quercetin,kaempferol,and multi stem cabbage chrysanthemum,Vascular endothelial growth factor A(VEGFA),interleukin-1β(IL-1β)and 10 key proteins such as tumor necrosis factor(TNF),enrichment analysis,Ilex cornuta folium treatment of NAFLD may be related to signaling pathways such as TNF,IL-17,advanced glycosylation product(AGE)-receptor for advanced glycosylation end products(RAGE),and molecular docking analysis showed good docking of key compounds and key targets.Conclusion Ilex cornuta folium treat NAFLD by modulating TNF,IL-17,AGE-RAGE,CLR and TLR signaling pathways.