Le Tuan Dat, Inoue Yoshihiro H
Insect Biomedical Research Center, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Antioxidants (Basel). 2021 Jun 7;10(6):924. doi: 10.3390/antiox10060924.
Sesamin, a major lignin in sesame seeds, possesses health-promoting properties. Sesamin feeding suppresses several aging-related phenotypes such as age-dependent accumulation of damaged proteins in the muscles and neuronal loss in the brains of adults with high levels of reactive oxygen species. Sesamin promotes the transcription of several genes that are responsible for oxidative stress, although the underlying mechanism remains unclear. Here, we aimed to demonstrate that sesamin mediates its action through activation of a transcription factor, Nrf2 (Cnc in ), essential for anti-aging oxidative stress response. Nrf2/Cnc activation was determined using the antioxidant response element, Green Fluorescence Protein reporter, that can monitor Nrf2/Cnc-dependent transcription. We observed strong fluorescence in the entire bodies, particularly in the abdomens and brains, of adult flies fed sesamin. Interestingly, Nrf2/Cnc was strongly activated in neuronal cells, especially in several neuron types, including glutamatergic and cholinergic, and some dopaminergic and/or serotonergic neurons but not in GABAergic neurons or the mushroom bodies of flies fed sesamin. These results indicate that the anti-aging effects of sesamin are exerted via activation of Nrf2/Cnc-dependent transcription to circumvent oxidative stress accumulation in several types of neurons of adult brains. Sesamin could be explored as a potential dietary supplement for preventing neurodegeneration associated with accumulation of oxidative stress.
芝麻素是芝麻籽中的一种主要木脂素，具有促进健康的特性。喂食芝麻素可抑制多种与衰老相关的表型，如在具有高水平活性氧的成年人中，肌肉中受损蛋白质随年龄增长的积累以及大脑中的神经元损失。芝麻素可促进几种负责氧化应激的基因的转录，但其潜在机制仍不清楚。在此，我们旨在证明芝麻素通过激活转录因子Nrf2（Cnc in）来介导其作用，Nrf2对抗衰老氧化应激反应至关重要。使用抗氧化反应元件绿色荧光蛋白报告基因来测定Nrf2/Cnc的激活情况，该报告基因可监测Nrf2/Cnc依赖性转录。我们观察到，喂食芝麻素的成年果蝇全身，尤其是腹部和大脑中出现强烈荧光。有趣的是，在喂食芝麻素的果蝇中，Nrf2/Cnc在神经元细胞中被强烈激活，特别是在几种神经元类型中，包括谷氨酸能和胆碱能神经元，以及一些多巴胺能和/或5-羟色胺能神经元，但在GABA能神经元或蘑菇体中未被激活。这些结果表明，芝麻素的抗衰老作用是通过激活Nrf2/Cnc依赖性转录来规避成年大脑中几种类型神经元的氧化应激积累。芝麻素可作为一种潜在的膳食补充剂进行探索，以预防与氧化应激积累相关的神经退行性变。
