Background

Polyphenols are phytochemicals that have been associated with therapeutic effects in stress-related disorders. Indeed, studies suggest that polyphenols exert significant neuroprotection against multiple neuronal injuries, including oxidative stress and neuroinflammation, but the mechanisms are unclear. Evidence indicates that polyphenol neuroprotection may be mediated by activation of Nrf2, a transcription factor associated with antioxidant and cell survival responses. On the other hand, in stress-linked disorders, Fkbp5 is a novel molecular target for treatment because of its capacity to regulate glucocorticoid receptor sensitivity. However, it is not clear the role Fkbp5 plays in polyphenol-mediated stress modulation. In this study, the neuroprotective effects and mechanisms of the naturally derived polyphenols xanthohumol and quercetin against cytotoxicity induced by corticosterone were investigated in primary cortical cells.

Methods

Primary cortical cells containing both neurons and astrocytes were pre-incubated with different concentrations of quercetin and xanthohumol to examine the neuroprotective effects of polyphenols on cell viability, morphology, and gene expression following corticosterone insult.

Results

Both polyphenols tested prevented the reduction of cell viability and alterations of neuronal/astrocytic numbers due to corticosterone exposure. Basal levels of Bdnf mRNA were also decreased after corticosterone insult; however, this was reversed by both polyphenol treatments. Interestingly, the Nrf2 inhibitor blocked xanthohumol but not quercetin-mediated neuroprotection. In contrast, we found that Fkbp5 expression is exclusively modulated by quercetin.

Conclusions

These results suggest that naturally derived polyphenols protect cortical cells against corticosterone-induced cytotoxicity and enhance cell survival via modulation of the Nrf2 pathway and expression of Fkbp5.

中文翻译：

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天然衍生的多酚可防止皮质酮引起的初级皮质神经元变化。

背景

多酚是与压力相关疾病的治疗效果相关的植物化学物质。事实上，研究表明多酚对多种神经元损伤具有显着的神经保护作用，包括氧化应激和神经炎症，但机制尚不清楚。证据表明，多酚神经保护作用可能是通过 Nrf2 的激活介导的，Nrf2 是一种与抗氧化和细胞存活反应相关的转录因子。另一方面，在压力相关疾病中，Fkbp5 是一种新的分子治疗靶点，因为它具有调节糖皮质激素受体敏感性的能力。然而，Fkbp5 在多酚介导的应激调节中的作用尚不清楚。在这项研究中，

方法

将含有神经元和星形胶质细胞的原代皮质细胞与不同浓度的槲皮素和黄腐酚一起预孵育，以检测多酚对皮质酮损伤后细胞活力、形态和基因表达的神经保护作用。

结果

所测试的两种多酚均能防止因皮质酮暴露而导致的细胞活力降低和神经元/星形胶质细胞数量的改变。皮质酮损伤后 Bdnf mRNA 的基础水平也降低；然而，这两种多酚处理都逆转了这一点。有趣的是，Nrf2 抑制剂阻断黄腐酚但不阻断槲皮素介导的神经保护作用。相反，我们发现 Fkbp5 表达完全由槲皮素调节。

结论

这些结果表明，天然来源的多酚保护皮质细胞免受皮质酮诱导的细胞毒性，并通过调节 Nrf2 通路和 Fkbp5 的表达来增强细胞存活。