Butein attenuates the cytotoxic effects of LPS-stimulated microglia on the SH-SY5Y neuronal cell line
Butein attenuates the cytotoxic effects of LPS-stimulated microglia on the SH-SY5Y neuronal cell line
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Butein 减弱 LPS 刺激的小胶质细胞对 SH-SY5Y 神经元细胞系的细胞毒性作用
DOI：
10.1016/j.ejphar.2019.172858
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发表时间：
2020-02-05
影响因子：
5
通讯作者：
Zhang, Haiying
中科院分区：
文献类型：
--
作者：
Liu, Yiheng;Fu, Yuan;Zhang, Haiying
神经炎症参与神经退行性疾病如阿尔茨海默病（AD）中的脑老化和神经元细胞死亡。Butein被认为具有抗炎、抗凋亡和抗癌作用。然而，很少有研究来评估Butein是否对神经元具有保护作用，并且尚未研究这种作用的潜在机制。在这里，我们研究的影响，Butein对SH-SY 5 Y神经母细胞瘤细胞生长的条件培养基从BV 2小胶质细胞，已被激活的脂多糖（LPS）作为神经炎症模型。我们发现，Butein预处理显着增加SH-SY 5 Y细胞的活力，在剂量依赖性的方式，通过抑制凋亡通常诱导的小胶质细胞条件培养基。SH-SY 5 Y细胞经小胶质细胞条件培养液处理后，ERK信号通路相关的mRNA表达和蛋白磷酸化水平上调，但被butein剂量依赖性逆转。免疫细胞化学和Western blot结果显示，BV 2-LPS条件培养基可诱导SH-SY 5 Y细胞核因子-κ B（NF-κ B）的反式激活，但在LPS作用前用Butein处理BV 2细胞可减弱这种激活。总的来说，我们的研究结果表明，Butein有效地减轻炎症损伤所造成的LPS条件培养基从小胶质细胞，可能是由于减少NF-κ B p65和ERK信号通路激活的反式激活活性，并提供证据，通过阻断小胶质细胞激活的负面后果的神经保护作用的Butein。
Neuroinflammation is involved in brain aging and neuronal cell death in neurodegenerative diseases such as Alzheimer's disease (AD). Butein has been suggested to have anti-inflammatory, anti-apoptotic, and anti-cancer effects. However, few studies have been done to evaluate whether butein exerts protective effects on neurons, and the potential mechanism for this effect has not been studied. Here, we examined the effect of butein on SH-SY5Y neuroblastoma cells grown with conditioned medium from BV2 microglia cells that had been activated by lipopolysaccharide (LPS) as a neuroinflammation model. We found butein pretreatment significantly increased SH-SY5Y cell viability in a dose-dependent manner by inhibiting the apoptosis normally induced by microglia-conditioned medium. SH-SY5Y cells treated with microglia-conditioned medium showed upregulated ERK signaling pathway-related mRNA expression and protein phosphorylation, which was dose-dependently reversed by butein. Immunocytochemistry and Western blot results showed that BV2-LPS conditioned medium-induced Nuclear factor kappaB (NF-kappa B) transactivational activity in SH-SY5Y cells, but this was attenuated by butein treatment of the BV2 cells prior to their exposure to LPS. Collectively, our results indicate that butein effectively mitigates inflammatory injury caused by LPS-conditioned medium from microglia, possibly due to reductions in the transactivational activity of NF-kappa B p65 and ERK signaling pathway activation, and provide evidence for a neuroprotective role of butein through blocking negative consequences of microglial activation.