Epigallocatechin gallate (EGCG) is one of polyphenol that is abundant in green tea. It has anti-oxidative activity and exerts neuroprotective effects in ischemic brain damage. Ischemic conditions induce oxidative stress and result in cell death. Thioredoxin is a small redox protein that plays an important role in the regulation of oxidation and reduction. This study was designed to investigate the regulation of thioredoxin by EGCG in ischemic brain damage. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia in male Sprague–Dawley rats. The EGCG (50 mg/kg) or was administered before MCAO surgical operation. Neurological behavior test, reactive oxygen species (ROS), and lipid peroxidation (LPO) measurement were performed 24 h after MCAO. The cerebral cortex was isolated for further experiments. EGCG alleviated MCAO-induced neurological deficits and increases in ROS and LPO levels. EGCG also ameliorated the decrease in thioredoxin expression by MCAO. This finding was confirmed using various techniques such as Western blot analysis, reverse transcription PCR, and immunofluorescence staining. Results of immunoprecipitation showed that MCAO decreases the interaction between apoptosis signal-regulating kinase 1 (ASK1) and thioredoxin, while EGCG treatment attenuates this decrease. EGCG also attenuated decrease of cell viability and thioredoxin expression in glutamate-exposed neuron in a dose-dependent manner. It alleviated the increase of caspase-3 by glutamate exposure. However, this effect of EGCG on caspase-3 change was weakened in thioredoxin siRNA-transfected neurons. These findings suggest that EGCG exerts a neuroprotective effect by regulating thioredoxin expression and modulating ASK1 and thioredoxin binding in ischemic brain damage.

表没食子儿茶素没食子酸酯（EGCG）是绿茶中含量丰富的多酚之一。它具有抗氧化活性，并在缺血性脑损伤中发挥神经保护作用。缺血条件诱导氧化应激并导致细胞死亡。硫氧还蛋白是一种小的氧化还原蛋白，在氧化和还原的调节中起重要作用。本研究旨在探讨 EGCG 在缺血性脑损伤中对硫氧还蛋白的调节作用。进行大脑中动脉闭塞（MCAO）以诱导雄性 Sprague-Dawley 大鼠的局灶性脑缺血。EGCG (50 mg/kg) 或在 MCAO 手术前给药。MCAO 后 24 小时进行神经行为测试、活性氧 (ROS) 和脂质过氧化 (LPO) 测量。大脑皮层被分离用于进一步的实验。EGCG 减轻了 MCAO 引起的神经功能缺损和 ROS 和 LPO 水平的增加。EGCG 还改善了 MCAO 对硫氧还蛋白表达的降低。使用各种技术（例如蛋白质印迹分析、逆转录 PCR 和免疫荧光染色）证实了这一发现。免疫沉淀结果表明，MCAO 降低了凋亡信号调节激酶 1 (ASK1) 和硫氧还蛋白之间的相互作用，而 EGCG 处理则减弱了这种降低。EGCG 还以剂量依赖性方式减弱谷氨酸暴露神经元中细胞活力和硫氧还蛋白表达的降低。它减轻了谷氨酸暴露引起的 caspase-3 的增加。然而，EGCG 对 caspase-3 变化的这种影响在硫氧还蛋白 siRNA 转染的神经元中减弱。