Green tea epigallocatechin gallate attenuate metabolic dysfunction-associated steatotic liver disease by regulation of pyroptosis.

IF 3.9 2区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Lipids in Health and Disease Pub Date : 2025-05-17 DOI:10.1186/s12944-025-02596-5

Jie Zhang, Shuangshuang Wang, Ting Zhang, Minghui Zi, Shuxiang Wang, Qiao Zhang

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引用次数: 0

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease, with other fat-liver diseases potentially progressing to cirrhosis and hepatocellular carcinoma. Our study aimed to alleviate MASLD by EGCG inhibiting oxidative stress-mediated pyroptosis in zebrafish.

Methods: The one month old wild-type zebrafh larval (50 per group) and three months old adult male zebrafish (15 per group) were treated with high-fat diet (HFD) feeding (powdered egg yolk) following by treatment with 25 μM EGCG for 15 days. Indicators related to liver damage, oxidative stress, inflammation, pyroptosis and aging were assessed using Oil Red O staining, H&E staining, commercial assay kits, enzyme-linked immunosorbent assay (ELISA) kits, and Western blot analysis.

Results: The results suggest that EGCG significantly reduced fatness, severe lipid deposition, triglyceride (TG), total cholesterol (TC) and free fatty acid (FFA) levels (p < 0.05). EGCG markedly reduced serum ALT, AST and ameliorated liver injury in zebrafish (p < 0.05). EGCG also showed an antioxidant effect by reducing reactive oxygen species (ROS) production malondialdehyde (MDA) and increasing superoxide dismutase (SOD) levels (p < 0.05). Moreover, EGCG obviously down-regulated the pro-inflammatory factors like tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18) levels (p < 0.05). EGCG indicated a significant upregulation involved in pyroptosis pathway, such as nuclear factor erythroid 2-related factor 2 (NRF2) and downregulated the expressions of nuclear factor-κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), as well as gasdermin D (GSDMD) (p < 0.01). Moreover, EGCG significantly improved aging-related markers induced by a HFD, including the level of senescence-associated β-Galactosidase (SA β-Gal) and expression of p53, p16, and p21 (p < 0.05), while ameliorating liver function in zebrafish.

Conclusions: These results suggest that EGCG may attenuate MASLD in larval and adult zebrafish induced by 15 consecutive days HFD, which is potentially mediated by modulating the Nrf2/NF-κB/NLRP3 signaling pathway which relieve pyroptosis.

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绿茶表没食子儿茶素没食子酸酯通过调节焦亡减轻代谢功能障碍相关的脂肪变性肝病。

背景：代谢功能障碍相关的脂肪变性肝病（MASLD）已成为最常见的慢性肝病，其他脂肪性肝病可能进展为肝硬化和肝细胞癌。我们的研究旨在通过EGCG抑制斑马鱼氧化应激介导的焦亡来缓解MASLD。方法：1月龄野生型斑马鱼幼鱼（每组50只）和3月龄成年雄性斑马鱼（每组15只）分别饲喂高脂饲料（蛋黄粉），然后用25 μM EGCG处理15 d。采用油红O染色、H&E染色、商业检测试剂盒、酶联免疫吸附试验（ELISA）试剂盒和Western blot分析评估肝损伤、氧化应激、炎症、焦亡和衰老相关指标。结果：EGCG可显著降低斑马鱼脂肪、重度脂质沉积、甘油三酯（TG）、总胆固醇（TC）和游离脂肪酸（FFA）水平(p)。结论：EGCG可能通过调节Nrf2/NF-κB/NLRP3信号通路，减轻斑马鱼连续15 d HFD诱导的MASLD。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lipids in Health and Disease 生物-生化与分子生物学

CiteScore

7.70

自引率

2.20%

发文量

122

审稿时长

3-8 weeks

期刊介绍： Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.