Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai 200030, China.
Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200030, China.
Molecules. 2022 Mar 17;27(6):1962. doi: 10.3390/molecules27061962.
Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.
越来越多的证据表明，川陈皮素（NOB）是一种很有前途的神经保护剂。星形胶质细胞的激活在神经退行性疾病中起着关键作用。因此，本研究旨在探讨 NOB 对星形胶质细胞激活的影响及其潜在机制。在这项研究中，体外培养星形胶质细胞，使其在缺氧损伤下暴露 24 小时以诱导激活。胶质纤维酸性蛋白（GFAP）被选为星形胶质细胞激活的标志物。为了评估 NOB 对激活星形胶质细胞迁移的影响，我们使用划痕愈合实验和 Transwell 迁移实验。此外，还测量了活性氧（ROS）、丙二醛（MDA）、线粒体膜电位、Nrf2 和 HO-1 的水平，以研究 NOB 在星形胶质细胞激活中的作用机制。我们发现，NOB 减轻了缺氧诱导的星形胶质细胞激活和 GFAP 表达的增加。同时，NOB 减轻了缺氧诱导的星形胶质细胞迁移。用 NOB 处理后，部分逆转了缺氧引起的氧化应激，包括减少 ROS 和 MDA 的产生。此外，NOB 显著改善了激活的星形胶质细胞中的线粒体功能障碍。最后，NOB 促进了 Nrf2 核易位和 HO-1 的表达，以应对持续的氧化损伤。我们的研究首次表明，NOB 减轻了体外缺氧诱导的星形胶质细胞激活，部分是通过改善氧化应激和线粒体功能障碍。这为 NOB 的神经保护作用提供了新的见解。
