Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan.
Molecules. 2020 Mar 3;25(5):1117. doi: 10.3390/molecules25051117.
(1) Background: Our published data have indicated that 1) auraptene (AUR), a citrus ingredient, has neuroprotective effects on the mouse brain, owing to its ability to suppress inflammation, such as causing a reduction in hyperactivation of microglia and astrocytes; 2) AUR has the ability to trigger phosphorylation (activation) of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) in neuronal cells; 3) AUR has the ability to induce glial cell line-derived neurotrophic factor (GDNF) synthesis/secretion in rat C6 glioma cells. The well-established fact that the ERK-CREB pathway plays an important role in the production of neurotrophic factors, including GDNF and brain-derived neurotrophic factor (BDNF), prompted us to investigate whether AUR would also have the ability to induce BDNF expression in neuronal cells. (2) Methods: Mouse neuroblastoma neuro2a cells were cultured and the effects of AUR on BDNF mRNA expression and protein content were evaluated by RT-PCR and ELISA, respectively. (3) Results: The levels of BDNF mRNA and secreted BDNF were significantly increased by AUR in a dose- and time-dependent manner in neuro2a cells. (4) Conclusion: The induction of BDNF in neuronal cells might be, in part, one of the mechanisms accounting for the neuroprotective effects of AUR.
(1) 背景：我们已发表的数据表明，1）柚皮素（AUR），一种柑橘成分，具有神经保护作用，这是因为它能够抑制炎症，如减少小胶质细胞和星形胶质细胞的过度激活；2）AUR 能够在神经元细胞中触发细胞外信号相关激酶（ERK）和 cAMP 反应元件结合蛋白（CREB）的磷酸化（激活）；3）AUR 能够诱导大鼠 C6 神经胶质瘤细胞中胶质细胞系衍生的神经营养因子（GDNF）的合成/分泌。ERK-CREB 途径在神经营养因子（包括 GDNF 和脑源性神经营养因子（BDNF）的产生中起着重要作用，这一事实已得到充分证实，这促使我们研究 AUR 是否也能够诱导神经元细胞中 BDNF 的表达。(2) 方法：培养小鼠神经母细胞瘤 neuro2a 细胞，并通过 RT-PCR 和 ELISA 分别评估 AUR 对 BDNF mRNA 表达和蛋白含量的影响。(3) 结果：AUR 以剂量和时间依赖的方式显著增加 neuro2a 细胞中 BDNF mRNA 和分泌型 BDNF 的水平。(4) 结论：神经元细胞中 BDNF 的诱导可能是 AUR 神经保护作用的部分机制之一。
