Department of Experimental Medicine (DIMES), University of Genoa, Viale Benedetto XV-1, 16132 Genova, Italy.
Department of Civil, Chemical and Environmental Engineering, University of Genoa, Pole of Chemical Engineering, via Opera Pia 15, 16145 Genoa, Italy.
Molecules. 2020 Sep 24;25(19):4385. doi: 10.3390/molecules25194385.
We have recently demonstrated that bioactive molecules, extracted by high pressure and temperature from olive pomace, counteract calcium-induced cell damage to different cell lines. Here, our aim was to study the effect of the same extract on murine cortical neurons, since the preservation of the intracellular Ca-homeostasis is essential for neuronal function and survival. Accordingly, we treated neurons with different stimuli in order to evoke cytotoxic glutamatergic activation. In these conditions, the high-pressure and temperature extract from olive pomace (HPTOPE) only abolished the effects of -methyl-d-aspartate (NMDA). Particularly, we observed that HPTOPE was able to promote the neuron rescue from NMDA-induced cell death. Moreover, we demonstrated that HPTOPE is endowed with the ability to maintain the intracellular Ca-homeostasis following NMDA receptor overactivation, protecting neurons from Ca-induced adverse effects, including aberrant calpain proteolytic activity. Moreover, we highlight the importance of the extraction conditions used that, without producing toxic molecules, allow us to obtain protecting molecules belonging to proanthocyanidin derivatives like procyanidin B2. In conclusion, we can hypothesize that HPTOPE, due to its functional and nontoxic properties on neuronal primary culture, can be utilized for future therapeutic interventions for neurodegeneration.
我们最近的研究表明,从橄榄渣中通过高压高温提取的生物活性分子可以抵抗钙离子诱导的不同细胞系的细胞损伤。在这里,我们的目的是研究相同提取物对鼠皮质神经元的影响,因为细胞内钙稳态的维持对于神经元的功能和存活至关重要。因此,我们用不同的刺激物处理神经元,以引发细胞毒性谷氨酸激活。在这些条件下,橄榄渣的高压高温提取物(HPTOPE)仅能消除 -甲基-d-天冬氨酸(NMDA)的作用。特别是,我们观察到 HPTOPE 能够促进神经元从 NMDA 诱导的细胞死亡中恢复。此外,我们证明 HPTOPE 具有在 NMDA 受体过度激活后维持细胞内钙稳态的能力,保护神经元免受 Ca 诱导的不良反应,包括异常钙蛋白酶蛋白水解活性。此外,我们强调了所使用的提取条件的重要性,这些条件不会产生有毒分子,使我们能够获得属于原花青素衍生物的保护分子,如原花青素 B2。总之,我们可以假设 HPTOPE 由于其对原代神经元培养物的功能和非毒性特性,可以用于未来的神经退行性疾病治疗干预。