Zhao Qiting, Ma Yantuanjin, Wang Shufen
Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China.
Antioxidants (Basel). 2025 Jun 12;14(6):723. doi: 10.3390/antiox14060723.
The occurrence of demyelination in the central nervous system (CNS) causes neurodegenerative lesions. The occurrence and development of demyelination involve multiple pathological mechanisms, including the generation of reactive oxygen species (ROS) caused by mitochondrial dysfunction in microglia and subsequent neuroinflammation. Scutellarin is a natural flavonoid drug with significant neuroprotective effects, including antioxidant, anti-inflammatory, and anti-apoptotic properties, and is widely used in the treatment of neurological diseases. However, the protective effects and mechanisms of scutellarin on demyelination have not yet been elucidated. This study aims to investigate the neuroprotective effects of scutellarin on demyelination and its underlying molecular mechanisms. Our results showed that treatment with scutellarin significantly alleviated Cuprizone-induced myelin damage, neuronal apoptosis, and neurological deficits in mice. In in vitro experiments, scutellarin significantly reduced Cuprizone-copper-induced pro-inflammatory microglia formation and inhibited the secretion of TNF-α, thereby reducing myelin cell damage. Mechanism studies revealed that scutellarin inhibited the secretion of TNF-α by microglia and alleviated myelin cell damage by reducing the excessive production of mitochondrial reactive oxygen species (Mito-ROS), reactive oxygen species (ROS), and malondialdehyde (MDA) induced by Cuprizone-copper in microglia. Finally, scutellarin improved mitochondrial dysfunction in microglia and significantly alleviated myelin cell damage by inhibiting the expression of p38MAPK. In conclusion, our findings demonstrate that scutellarin exerts significant neuroprotective effects on Cuprizone-induced mice by improving mitochondrial dysfunction in microglia, thereby reducing inflammatory responses. This effect is closely associated with the inhibition of the p38MAPK pathway.
中枢神经系统（CNS）中脱髓鞘的发生会导致神经退行性病变。脱髓鞘的发生和发展涉及多种病理机制，包括小胶质细胞线粒体功能障碍引起的活性氧（ROS）生成以及随后的神经炎症。灯盏花素是一种具有显著神经保护作用的天然黄酮类药物，具有抗氧化、抗炎和抗凋亡特性，广泛用于治疗神经系统疾病。然而，灯盏花素对脱髓鞘的保护作用及其机制尚未阐明。本研究旨在探讨灯盏花素对脱髓鞘的神经保护作用及其潜在的分子机制。我们的结果表明，灯盏花素治疗可显著减轻小鼠中由双环己酮草酰二腙诱导的髓鞘损伤、神经元凋亡和神经功能缺损。在体外实验中，灯盏花素显著减少了双环己酮草酰二腙 - 铜诱导的促炎性小胶质细胞形成，并抑制了肿瘤坏死因子 -α（TNF-α）的分泌，从而减少了髓鞘细胞损伤。机制研究表明，灯盏花素通过减少双环己酮草酰二腙 - 铜在小胶质细胞中诱导的线粒体活性氧（Mito-ROS）、活性氧（ROS）和丙二醛（MDA）的过量产生，抑制小胶质细胞分泌TNF-α并减轻髓鞘细胞损伤。最后，灯盏花素改善了小胶质细胞中的线粒体功能障碍，并通过抑制p38丝裂原活化蛋白激酶（p38MAPK）的表达显著减轻了髓鞘细胞损伤。总之，我们的研究结果表明，灯盏花素通过改善小胶质细胞中的线粒体功能障碍，从而减少炎症反应，对双环己酮草酰二腙诱导的小鼠发挥显著的神经保护作用。这种作用与抑制p38MAPK途径密切相关。
