基于网络药理学和分子对接技术的化滞柔肝颗粒治疗非酒精性脂肪性肝病的作用机制研究

Mechanism of Huazhi Rougan Granules in the Treatment of Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接技术,探讨化滞柔肝颗粒治疗非酒精性脂肪性肝病(NAFLD)的作用机制。方法:利用中药系统药理学数据库与分析平台、中医药百科全书数据库对药物化合物靶点进行筛选,利用GeneCards数据库、DigSee数据库等对NAFLD疾病靶点进行筛选,进而构建相关网络。运用R语言对共有靶点进行基因本体功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后将关键化合物与核心靶点进行分子对接验证,利用Pymol软件对结果进行可视化处理。结果:预测得到的核心化合物为槲皮素、山柰酚、木犀草素和汉黄芩素,核心靶点为信号转导及转录激活因子3、JUN、白细胞介素6、肿瘤坏死因子、CXC趋化因子配体8、血管内皮生长因子A、表皮生长因子、白细胞介素1β、趋化因子配体2和肿瘤蛋白p53。KEGG通路富集分析结果显示,作用的通路与传染病、免疫系统、内分泌和代谢性疾病相关,如糖尿病并发症中的AGE-RAGE信号通路、人巨细胞病毒感染等信号通路。结论:本研究结果验证和预测了化滞柔肝颗粒治疗NAFLD的作用机制,为进一步深入揭示其作用机制奠定了良好基础。

OBJECTIVE:To probe into the potential mechanism of Huazhi Rougan Granules in the treatment of non-alcoholic fatty liver disease(NAFLD)based on network pharmacology and molecular docking.METHODS:The drug compound targets were screened by using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform and the Encyclopedia of Chinese Medicine database,the disease targets of NAFLD were screened by using the GeneCards database and DigSee database,so that the related networks were constructed.Gene ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the shared targets by using R language.Finally,the molecular docking verification of key compounds and core targets was conducted,and the results were visualized by using Pymol software.RESULTS:The predicted core compounds were quercetin,kaempferol,luteolin and wogonin,the core targets were signal transduction and activating transcription factor 3,JUN,interleukin-6,tumor necrosis factor,CXCL8,vascular endothelial growth factor A,epidermal growth factor,interleukin-1β,chemokine ligand 2 and TP53.The results of KEGG pathway enrichment analysis showed that the pathways were associated with infectious diseases,immune system,endocrine and metabolic diseases,such as the AGE-RAGE signaling pathway,human cytomegalovirus infection and other signaling pathways in diabetic complications.CONCLUSIONS:The results of this study have initially validated and predicted the mechanism of Huazhi Rougan granules in the treatment of NAFLD,which laid a good foundation for further insight into its mechanism of action.