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首页> 外文期刊>The European Journal of Neuroscience >Oral administration of the flavanol (-)-epicatechin bolsters endogenous protection against focal ischemia through the Nrf2 cytoprotective pathway
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Oral administration of the flavanol (-)-epicatechin bolsters endogenous protection against focal ischemia through the Nrf2 cytoprotective pathway

机译：黄烷醇（-）-表儿茶素的口服给药可通过Nrf2细胞保护途径增强对局灶性局部缺血的内源性保护

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Consumption of flavan-3-ols, notably (-)-epicatechin (EC), has been highly recommended in complementary and alternative medicine (CAM) due to reports that flavan-3-ols boost antioxidant activity, support vascular function, and prevent cardiovascular disease. To date, in vivo efficacy and mechanisms of action for many CAM therapies, including EC, remain elusive in brain ischemia. In contrast to its purported direct antioxidant role, we hypothesized protection through activation of the endogenous transcrip-tional factor Nrf2. To screen cellular protection and investigate Nrf2 activation, we adopted a pretreatment paradigm using enriched primary neuronal cultures from mice and washed out EC prior to oxygen glucose deprivation to attenuate direct antioxidant effects. EC protected primary neurons from oxygen glucose deprivation by increasing neuronal viability (40.2 ± 14.1%) and reducing protein oxidation, effects that occurred concomitantly with increased Nrf2-responsive antioxidant protein expression. We also utilized wildtype and Nrf2 C57BL/6 knockout mice in a permanent model of focal brain ischemia to evaluate glial cell regulation and complex sensorimotor functioning. EC-treated wildtype mice displayed a reduction or absence of forelimb motor coordination impairments that were evident in vehicle-treated mice. This protection was associated with reduced anatomical injury (54.5 ± 8.3%) and microglia/macrophage activation/recruitment (56.4 ± 13.0%). The protective effects elicited by EC in both model systems were abolished in tissues and neuronal cultures from Nrf2 knockout mice. Together, these data demonstrate EC protection through Nrf2 and extend the benefits to improved performance on a complex sensorimotor task, highlighting the potential of flavan-3-ols in CAM approaches in minimizing subsequent stroke injury.
机译：强烈建议在补充和替代药物（CAM）中食用黄烷-3-醇，尤其是（-）-表儿茶素（EC），因为据报道黄烷-3-醇可增强抗氧化活性，支持血管功能并预防心血管疾病疾病。迄今为止，包括脑电图在内的许多CAM疗法的体内功效和作用机制在脑缺血中仍然难以捉摸。与它声称的直接抗氧化剂作用相反，我们推测是通过激活内源转录因子Nrf2来提供保护。为了筛选细胞保护作用并研究Nrf2激活，我们采用了预处理范例，该范例使用了来自小鼠的丰富的原代神经元培养物，并在剥夺氧气葡萄糖之前洗掉了EC，以减弱直接的抗氧化作用。 EC通过增加神经元生存力（40.2±14.1％）和减少蛋白质氧化来保护原代神经元免受氧葡萄糖剥夺，这种影响与Nrf2反应性抗氧化剂蛋白质表达的增加同时发生。我们还利用局灶性脑缺血的永久模型中的野生型和Nrf2 C57BL / 6基因敲除小鼠来评估神经胶质细胞调节和复杂的感觉运动功能。 EC处理的野生型小鼠表现出减少或不存在前肢运动协调障碍，这在载体处理的小鼠中很明显。这种保护与减少的解剖损伤（54.5±8.3％）和小胶质细胞/巨噬细胞激活/招募（56.4±13.0％）有关。 EC在两种模型系统中引起的保护作用在Nrf2基因敲除小鼠的组织和神经元培养物中均被取消。这些数据共同证明了通过Nrf2可以保护EC，并扩大了其在复杂的感觉运动任务中的性能改善所带来的好处，从而突出了CAM方法中黄烷-3-醇在最大程度减少后续中风伤害方面的潜力。

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