PDF(Pubmed)
Abstract：
Cannabidiol (CBD) appears to possess some neuroprotective properties, but experimental data are still inconsistent. Therefore, this in vitro study aimed to compare the effects of CBD in a wide range of concentrations on oxidative stress and excitotoxic-related cell damage. Results showed that low concentrations of CBD ameliorated the H2O2-evoked cell damage of primary cortical neuronal cell culture. However, higher concentrations of CBD alone (5-25 μM) decreased the viability of cortical neurons in a concentration-dependent manner and aggravated the toxic effects of hydrogen peroxide (H2O2). Neuroprotection mediated by CBD in primary neurons against H2O2 was not associated with a direct influence on ROS production nor inhibition of caspase-3, but we found protective effects of CBD at the level of mitochondrial membrane potential and DNA fragmentation. However, CBD had no protective effect on the glutamate-induced cell damage of cortical neurons, and in higher concentrations, it enhanced the toxic effects of this cell-damaging factor. Likewise, CBD, depending on its concentration, at least did not affect or even enhance cortical cellular damage exposed to oxygen-glucose deprivation (OGD). Finally, we showed that CBD in submicromolar or low micromolar concentrations significantly protected human neuronal-like SH-SY5Y cells against H2O2- and 6-hydroxydopamine (6-OHDA)-induced cell damage. Our data indicate that CBD has a dual effect on oxidative stress-induced neuronal death-in low concentrations, it is neuroprotective, but in higher ones, it may display neurotoxic activity. On the other hand, in excitotoxic-related models, CBD was ineffective or enhanced cell damage. Our data support the notion that the neuroprotective effects of CBD strongly depend on its concentration and experimental model of neuronal death.
摘要：
大麻二酚（CBD）似乎具有一些神经保护特性，但是实验数据仍然不一致。因此,这项体外研究旨在比较各种浓度的CBD对氧化应激和兴奋性毒性相关细胞损伤的影响.结果表明，低浓度的CBD可以改善原代皮质神经元细胞培养物中H2O2引起的细胞损伤。然而,单独使用较高浓度的CBD（5-25μM）以浓度依赖性方式降低了皮质神经元的活力，并加剧了过氧化氢（H2O2）的毒性作用。CBD在原代神经元中针对H2O2介导的神经保护与对ROS产生的直接影响或对caspase-3的抑制无关，但我们发现CBD在线粒体膜电位和DNA片段化水平上的保护作用。然而,CBD对谷氨酸诱导的皮质神经元细胞损伤没有保护作用，在更高的浓度下，它增强了这种细胞损伤因子的毒性作用。同样，CBD,取决于它的浓度，至少没有影响甚至增强暴露于氧-葡萄糖剥夺（OGD）的皮质细胞损伤。最后,我们表明，亚微摩尔或低微摩尔浓度的CBD可显着保护人神经元样SH-SY5Y细胞免受H2O2-和6-羟基多巴胺（6-OHDA）诱导的细胞损伤。我们的数据表明，CBD在低浓度下对氧化应激诱导的神经元死亡具有双重作用，它具有神经保护作用，但是在更高的地方，它可能显示神经毒性活性。另一方面,在兴奋毒性相关模型中，CBD无效或细胞损伤增强。我们的数据支持以下观点：CBD的神经保护作用强烈取决于其浓度和神经元死亡的实验模型。
