A Bioactive Olive Pomace Extract Prevents the Death of Murine Cortical Neurons Triggered by NMDAR Over-Activation

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-09, Vol.25 (19), p.4385
• Main Authors: Franchi, Alice, Pedrazzi, Marco, Casazza, Alessandro Alberto, Millo, Enrico, Damonte, Gianluca, Salis, Annalisa, Liessi, Nara, Onofri, Franco, Marte, Antonella, Casagrande, Silvia, De Tullio, Roberta, Perego, Patrizia, Averna, Monica
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biflavonoids - chemistry; Biflavonoids - pharmacology; Biocompatibility; Biological activity; Calcium (intracellular); Calcium homeostasis; Calcium ions; Calcium Signaling - drug effects; Calpain; Catechin - chemistry; Catechin - pharmacology; Cell culture; Cell death; Cell Death - drug effects; Cell lines; Cells, Cultured; Cytotoxicity; Glutamate receptors; Glutamatergic transmission; Glutamic acid receptors (ionotropic); High pressure; Homeostasis; Intracellular; Kinases; Mice; N-Methyl-D-aspartic acid receptors; N-Methylaspartate - adverse effects; N-Methylaspartate - pharmacology; Neurodegeneration; neuron primary culture; Neurons; Neurons - metabolism; Neurons - pathology; NMDAR; Olea - chemistry; olive pomace extract; Physiology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polyphenols; proanthocyanidins; Proanthocyanidins - chemistry; Proanthocyanidins - pharmacology; Proteolysis; Receptors, N-Methyl-D-Aspartate - metabolism; Therapeutic applications
• ISSN: 1420-3049; 1420-3049
• 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.