Neuroinflammation is crucial for the pathophysiological hallmarks of many neurodegenerative disorders. Hyperactivated microglia has long been implicated as a detrimental player in regulating unresolvable inflammatory insults which cause damage to neurons. In the context of acrylamide (ACR) neurotoxicity, microglia activation is documented to correlate with ACR-adduct formation in the presynaptic neurons. Thus, inhibition of inflammatory mediators through vital candidate is greatly warranted to retard the disease progression. In the present study, we investigated, whether vitexin, a C-glycosylated flavone, with anti-inflammatory activity, could inhibit ACR-induced neuroinflammation-like behavior in zebrafish larvae. ACR was exposed at a dose 1 mM to 3 days post fertilization (dpf) zebrafish larvae for 3 days, whereas vitexin (10 μM) was treated for 24 h. After vitexin treatment, a series of histopathology, behavioral tests and molecular analyses were measured. Our data show that ACR larvae exhibited abnormal morphologies in brain cartilage and histological patterns. At behavioral levels, motor function was altered while the expression of pro-inflammatory mediator levels was markedly up-regulated in ACR larvae. Further, we validated the enhanced CDK5 activity is known to trigger microglia activation, also we found reduced expressions of neuroplasticity (CREB1 and ATF1) and antioxidant response makers (Nrf2, SOD-1 and CAT) in ACR intoxicated larvae. Interestingly, vitexin treatment markedly alleviated ACR-induced histological and behavioral changes in zebrafish larvae. Moreover, vitexin effectively inhibited CDK5 expression, and also hampered the release of pro-inflammatory mediators in ACR larvae. Finally, vitexin treatment rescued the loss of neuroplasticity markers along with enhanced antioxidant markers in ACR larvae. Taken together, results in the present study showed the possibility of vitexin as a potential therapeutic drug in the suppression of neuroinflammation.

中文翻译：

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Vitexin抑制丙烯酰胺诱导的神经炎症，并改善斑马鱼幼虫的行为变化。

神经炎症对于许多神经退行性疾病的病理生理标志至关重要。长期以来，高活化的小胶质细胞一直被认为是调节无法解决的炎症损伤的有害因素，这些炎症损伤会损害神经元。在丙烯酰胺（ACR）的神经毒性中，小胶质细胞的活化与突触前神经元中ACR加合物的形成有关。因此，非常有必要通过重要的候选物抑制炎症介质来延缓疾病的进展。在本研究中，我们调查了具有抗炎活性的维生素C（一种C-糖基化的黄酮）是否能抑制斑马鱼幼虫中ACR诱导的神经炎症样行为。受精后（dpf）斑马鱼幼虫在1 dM至3天后暴露ACR 3天，而Vitexin（10μM）处理24小时。葡萄黄素处理后，进行了一系列的组织病理学，行为学测试和分子分析。我们的数据表明，ACR幼虫在脑软骨和组织学模式中表现出异常的形态。在行为水平上，运动功能发生改变，而促炎介质水平的表达在ACR幼虫中明显上调。此外，我们验证了增强的CDK5活性已知会触发小胶质细胞活化，还发现ACR致毒幼虫中神经可塑性（CREB1和ATF1）和抗氧化剂反应产生剂（Nrf2，SOD-1和CAT）的表达降低。有趣的是，葡萄黄素处理显着减轻了斑马鱼幼虫中ACR诱导的组织学和行为变化。此外，vitexin有效抑制CDK5表达，并且还阻碍了ACR幼虫中促炎性介质的释放。最后，葡萄黄素治疗挽救了ACR幼虫中神经可塑性标志物的丢失以及抗氧化剂的增强。两者合计，本研究的结果表明，vitexin作为抑制神经炎症的潜在治疗药物的可能性。