Ding Shi-Bin, Chu Xiao-Lei, Jin Yu-Xuan, Jiang Jin-Jin, Zhao Xiao, Yu Min
Jiangsu Vocational College of Medicine, Yancheng, China.
Front Pharmacol. 2023 Mar 21;14:1148814. doi: 10.3389/fphar.2023.1148814. eCollection 2023.
Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice. Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. , steatotic L-02 cells were used to explore the underlying mechanism. In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells. Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes.
非酒精性脂肪性肝病（NAFLD）是一种慢性进展性肝病，与代谢紊乱高度相关，由高脂饮食（HFD）诱发。最近，表没食子儿茶素没食子酸酯（EGCG）被认为是绿茶中的一种具有保护作用的生物活性多酚，能够预防非酒精性脂肪性肝病，但其分子机制仍不清楚。铁死亡在非酒精性脂肪性肝病的进展中起关键作用，但表没食子儿茶素没食子酸酯抑制铁死亡的实验证据有限。因此，我们的研究旨在探讨表没食子儿茶素没食子酸酯对肝脏铁死亡的影响及其机制，以减轻高脂饮食喂养小鼠的肝损伤。将50只雄性C57BL/6小鼠分为标准饲料组（SCD）、高脂饮食组，或高脂饮食并给予表没食子儿茶素没食子酸酯或铁抑素-1（一种铁死亡特异性抑制剂）组，喂养12周。检测肝损伤、脂质蓄积、肝脂肪变性、氧化应激、铁过载及铁死亡标记蛋白。此外，使用脂肪变性的L-02细胞来探究潜在机制。在我们的研究中，我们发现表没食子儿茶素没食子酸酯在高脂饮食诱导的非酒精性脂肪性肝病小鼠模型中显著减轻了肝损伤、脂质蓄积、氧化应激、肝脂肪变性，降低了铁过载并抑制了铁死亡。在体外实验中，使用铁抑素-1和线粒体活性氧（MtROS）清除剂（Mito-TEMPO），我们发现表没食子儿茶素没食子酸酯通过降低脂肪变性的L-02细胞中线粒体活性氧水平，显著减轻了氧化应激并抑制了铁死亡。综上所述，我们的结果表明，表没食子儿茶素没食子酸酯可能通过抑制线粒体活性氧介导的肝脏铁死亡对肝脏脂毒性发挥保护作用。我们的研究结果为非酒精性脂肪性肝病病理过程的预防和治疗策略提供了新的见解。
