Fisetin, a natural flavonoid, has neuroprotection properties in many brain injury models. However, its role in traumatic brain injury (TBI) has not been fully explained. In the present study, we aimed to explore the neuroprotective effects of fisetin in a mouse model of TBI. We found that fisetin improved neurological function, reduced cerebral edema, attenuated brain lesion and ameliorated blood-brain barrier (BBB) disruption after TBI. Moreover, the up-regulation of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were reversed by fisetin treatment. Furthermore, administration of fisetin suppressed neuron cell death and apoptosis, increased the expression of B-cell lymphoma 2 (Bcl-2), while decreased the expression of Bcl-2-associated X protein (Bax) and caspase-3 after TBI. In addition, fisetin activated the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway following TBI. However, fisetin only failed to suppress oxidative stress in Nrf2^−/− mice. In conclusion, our data provided the first evidence that fisetin played a critical role in neuroprotection after TBI partly through the activation of the Nrf2-ARE pathway.

Fisetin是一种天然的类黄酮，在许多脑损伤模型中均具有神经保护作用。但是，其在创伤性脑损伤（TBI）中的作用尚未得到充分的解释。在本研究中，我们旨在探讨非瑟酮在TBI小鼠模型中的神经保护作用。我们发现，fisetin改善了TBI后的神经功能，减轻了脑水肿，减轻了脑病变并改善了血脑屏障（BBB）破坏。此外，通过非瑟酮处理逆转了丙二醛（MDA）的上调和谷胱甘肽过氧化物酶（GPx）的活性。此外，非瑟酮的抑制抑制了神经元细胞的死亡和凋亡，增加了TBI后B细胞淋巴瘤2（Bcl-2）的表达，同时降低了Bcl-2相关X蛋白（Bax）和caspase-3的表达。此外，Fisetin在TBI后激活了核因子红系2相关因子2（Nrf2）-抗氧化反应元件（ARE）途径。但是，非瑟汀只能抑制Nrf2的氧化应激^-/-小鼠。总之，我们的数据提供了第一个证据，证明非瑟酮在TBI后部分通过Nrf2-ARE途径的激活在神经保护中起着关键作用。