First School of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Medicine (Baltimore). 2023 Oct 20;102(42):e35460. doi: 10.1097/MD.0000000000035460.
This study aimed to use network pharmacology to investigate the molecular mechanisms and potential targets of naringenin (NR) for nonalcoholic fatty liver disease (NAFLD) treatment to offer new drug development ideas.
The structure and compound information of NR were obtained from PubChem and the traditional Chinese medicine system pharmacology database and analysis platform. The traditional Chinese medicine system pharmacology database and analysis platform Database, Comparative Toxicogenomics Database and Encyclopedia of Traditional Chinese Medicine Database were then used to predict the related targets of NR. Online mendelian inheritance in man, Disgenet, Gene cards, The therapeutic target database and Drug bank were used to screen NAFLD targets, and the intersection analysis was performed with the targets of NR active components to obtain the targets of NR in the treatment of NAFLD. The protein-protein interaction network of therapeutic targets was constructed by protein-protein interaction networks functional enrichment analysis 11.0, and gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of therapeutic targets was performed by Metascape platform.
In this study, 171 NR targets and 1748 potential targets of NAFLD were screened, and 89 crossover targets and 16 core targets were screened and finally obtained. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), including 389 biological process, 6 cell composition and 30 molecular function. A total of 137 signaling pathways were obtained by Kyoto encyclopedia of genes and genomes pathway enrichment and screening (P < .05). The core targets of NR in the treatment of NAFLD are TP53, CASP3, PRKCA, AKT1, RELA, PPARG, NCOA2, CYP1A1, ESR1, MAPK3, STAT3, JAK1, MAPK1, TNF, PPARA and PRKCB. Enrichment analysis showed that NR mainly involved in biological processes such as cellular response to nitrogen compound, regulation of miRNA transcription and negative regulation of miRNA-mediated gene silencing. It regulates Hepatitis B, Lipid and atherosclerosis, cytomegalovirus infection, Hepatitis C, AGE-RAGE signaling pathway in diabetic patients complications and other ways play a role in the treatment of NAFLD.
The therapeutic effect of NR on NAFLD has the characteristics of multi-targets and multi-pathways, which provides a preliminary theoretical basis for clinical trials and the development of new drugs.
本研究旨在采用网络药理学方法探讨柚皮素（NR）治疗非酒精性脂肪性肝病（NAFLD）的分子机制和潜在靶点，为新药研发提供思路。
从 PubChem 和中药系统药理学数据库与分析平台获取 NR 的结构和化合物信息，利用中药系统药理学数据库与分析平台数据库、比较毒理学基因组学数据库和中药综合数据库预测 NR 的相关靶点，利用在线孟德尔遗传数据库、Disgenet、基因卡片、治疗靶点数据库和药物银行筛选 NAFLD 靶点，并与 NR 活性成分的靶点进行交集分析，获得 NR 治疗 NAFLD 的靶点。利用 STRING 数据库构建治疗靶点的蛋白质-蛋白质相互作用网络，采用 Metascape 平台对治疗靶点进行基因本体（GO）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。
本研究共筛选出 171 个 NR 靶点和 1748 个潜在的 NAFLD 靶点，筛选出 89 个交集靶点和 16 个核心靶点。GO 功能富集分析共得到 176 个条目（P<0.05），包括 389 个生物过程、6 个细胞组成和 30 个分子功能；KEGG 通路富集分析共得到 137 条信号通路（P<0.05）。NR 治疗 NAFLD 的核心靶点有 TP53、CASP3、PRKCA、AKT1、RELA、PPARG、NCOA2、CYP1A1、ESR1、MAPK3、STAT3、JAK1、MAPK1、TNF、PPARA 和 PRKCB。富集分析显示，NR 主要参与细胞对含氮化合物的反应、miRNA 转录的调节以及 miRNA 介导的基因沉默的负调控等生物学过程，通过调控乙型肝炎、脂类与动脉粥样硬化、巨细胞病毒感染、丙型肝炎、糖尿病患者并发症的 AGE-RAGE 信号通路等发挥治疗 NAFLD 的作用。
NR 治疗 NAFLD 具有多靶点、多通路的特点，为临床研究和新药开发提供了初步的理论依据。
