Lin Hui-Hsuan, Wu Pei-Tzu, Liang Yu-Hsuan, Lee Ming-Shih, Chen Jing-Hsien
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 40201, Taiwan.
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
Int J Mol Sci. 2025 Aug 6;26(15):7612. doi: 10.3390/ijms26157612.
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (-)-epicatechin gallate (ECG). Despite ECG's well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly ( < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant ( < 0.01) decrease in oxidative stress by 83%, and a marked ( < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes.
代谢功能障碍相关脂肪性肝病(MASLD)始于肝脏脂质蓄积并引发胰岛素抵抗。叶提取物具有抗氧化和抗动脉粥样硬化活性,且富含(-)-表儿茶素没食子酸酯(ECG)。尽管ECG具有众所周知的药理活性,其总抗氧化能力也强于其他儿茶素,但其对MASLD的调节作用此前尚未得到充分描述。因此,本研究试图评估从叶中分离出的ECG对肝细胞异常脂质和葡萄糖代谢的抗MASLD潜力。首先,使用油酸(OA)作为实验模型来诱导人原代肝细胞中的脂质代谢紊乱。用ECG处理可显著(<0.05)减少OA诱导的细胞脂质蓄积。尼罗红染色显示,与OA组相比,在测试的ECG剂量下,抑制率分别为29%、61%和82%。ECG的有益作用与通过靶向AMPK下调SREBPs/HMGCR以及上调PPARα/CPT1有关。此外,在胰岛素信号阻断的OA暴露肝细胞中,0.4µM的ECG可使氧化应激显著(<0.01)降低83%,糖原合成显著(<0.05)增加145%。机制分析表明,如AMPK抑制剂所证实的,ECG的脂质和葡萄糖代谢稳态可能通过调节脂肪生成、脂肪酸β氧化和胰岛素抵抗来介导。这些结果表明ECG是肝细胞脂质和碳水化合物代谢紊乱的双重调节剂。