Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, 637000, China.
Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, China.
Biochem Biophys Res Commun. 2024 Nov 19;734:150424. doi: 10.1016/j.bbrc.2024.150424. Epub 2024 Jul 18.
To explore the therapeutic effects along with the molecular mechanisms of epigallocatechin gallate (EGCG) in non-alcoholic fatty liver disease (NAFLD) treatment using network pharmacology as well as animal experiments. Firstly, the Traditional Chinese Medicine (TCM) Systems Pharmacology Database was searched to identify the potential targets of EGCG. The DisGeNET Database was used to screen the potential targets of NAFLD. The GeneCards Database was searched to identify related genes involved in pyroptosis. Subsequently, the intersecting genes of EGCG targeting pyroptosis to regulate NAFLD were obtained using a Venn diagram. Simultaneously, the aforementioned intersecting genes were used to construct a drug-disease target protein-protein interaction (PPI) network. The DAVID database was adopted for Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The main pathway-target network was determined. Next, the potential mechanism of EGCG targeting pyroptosis to regulate NAFLD was investigated and validated through in vivo experiments. 626 potential targets of EGCG, 447 target genes of NAFLD, and 568 potential targets of pyroptosis were identified. The number of common targets between EGCG, NAFLD, and pyroptosis was 266. GO biological process items and 92 KEGG pathways were determined based on the analysis results. Animal experiments demonstrated that EGCG could ameliorate body weight, glucolipid metabolism, steatosis, and liver injury, enhance insulin sensitivity, and improve glucose tolerance in NAFLD mice through the classical pathway of pyroptosis. EGCG could effectively treat NAFLD through multiple targets and pathways. It was concluded that EGCG ameliorates hepatocyte steatosis, pyroptosis, dyslipidemia, and inflammation in NAFLD mice fed a high-fat diet (HFD), and the protective mechanism could be associated with the NLRP3-Caspase-1-GSDMD classical pyroptosis pathway.
采用网络药理学和动物实验方法，探讨表没食子儿茶素没食子酸酯（EGCG）治疗非酒精性脂肪性肝病（NAFLD）的疗效及分子机制。首先，利用中药系统药理学数据库（TCM）系统药理学数据库检索 EGCG 的潜在靶点。利用 DisGeNET 数据库筛选 NAFLD 的潜在靶点。利用 GeneCards 数据库搜索与细胞焦亡相关的基因。然后，通过 Venn 图获得 EGCG 靶向细胞焦亡调节 NAFLD 的交集基因。同时，利用上述交集基因构建药物-疾病靶点蛋白-蛋白相互作用（PPI）网络。采用 DAVID 数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。确定主要的通路-靶标网络。接下来，通过体内实验研究和验证 EGCG 通过靶向细胞焦亡调节 NAFLD 的潜在机制。鉴定出 626 个 EGCG 的潜在靶点、447 个 NAFLD 的靶基因和 568 个细胞焦亡的潜在靶点。EGCG、NAFLD 和细胞焦亡的共同靶点有 266 个。根据分析结果，确定了 GO 生物学过程项目和 92 个 KEGG 通路。动物实验表明，EGCG 可通过经典的细胞焦亡途径改善 NAFLD 小鼠的体重、糖脂代谢、脂肪变性和肝损伤，提高胰岛素敏感性，改善葡萄糖耐量。EGCG 可通过多种靶点和途径有效治疗 NAFLD。研究结果表明，EGCG 可改善高脂饮食喂养的 NAFLD 小鼠的肝细胞脂肪变性、细胞焦亡、血脂异常和炎症，其保护机制可能与 NLRP3-Caspase-1-GSDMD 经典细胞焦亡途径有关。
