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

Alice Franchi,Enrico Millo,Silvia Casagrande,Alessandro Alberto Casazza,Roberta De Tullio,Annalisa Salis,Franco Onofri,Gianluca Damonte,Antonella Marte,Nara Liessi,Patrizia Perego,Monica Averna,Marco Pedrazzi

doi:10.3390/molecules25194385

Alice Franchi, Enrico Millo + Show 11 more

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Journal: Molecules	Publication Date: Sep 24, 2020
Citations: 4	License type: CC BY 4.0

Affiliation: University of Genoa, Ospedale Policlinico San Martino

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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 Ca2+-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 N-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 Ca2+-homeostasis following NMDA receptor overactivation, protecting neurons from Ca2+-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.

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Growing evidence [1,2,3,4,5] has shown that a dietary pattern inspired by the Mediterranean diet (MD)principles is associated with numerous health benefits, such as protecting against neurodegeneration.The beneficial effects of MD are probably due to the abundant consumption of extra virgin olive oil (EVOO), known to be rich in phenolic compounds and endowed with different nutritional propertiesMolecules 2020, 25, 4385; doi:10.3390/molecules25194385 www.mdpi.com/journal/moleculesMolecules 2020, 25, 4385 and health effects [6]
This result suggests that high-pressure and temperature extract from olive pomace (HPTOPE), being not able to protect neurons from death caused by nonspecific glutamate stimulation, could probably act through a mechanism that involves other or more precise molecular targets
In neurons treated with NMDA in the presence of HPTOPE, we observed, further than the preservation of the native form of neuronal nitric oxide synthase (nNOS), a trend for an accumulation of the activated 130 kDa nNOS form, confirming that HPTOPE prevents the aberrant proteolytic activity of the calcium-dependent protease calpain, allowing it to maintain its physiological function. All these results definitely indicate that HPTOPE is able to protect neurons from those intracellular calcium-induced harmful events promoted by the overactivation of NMDAR, including the aberrant calpain activation

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Introduction

Growing evidence [1,2,3,4,5] has shown that a dietary pattern inspired by the Mediterranean diet (MD)principles is associated with numerous health benefits, such as protecting against neurodegeneration.The beneficial effects of MD are probably due to the abundant consumption of extra virgin olive oil (EVOO), known to be rich in phenolic compounds and endowed with different nutritional propertiesMolecules 2020, 25, 4385; doi:10.3390/molecules25194385 www.mdpi.com/journal/moleculesMolecules 2020, 25, 4385 and health effects [6]. The phenolic compounds include a wide variety of structures expanding from the simplest structures, such as phenolic acids and alcohols, to the most complex oligomeric ones, such as proanthocyanidins. All these compounds are present in olive oil production wastes, such as olive pomace and olive mill waste waters [7]. Numerous studies have shown that the polyphenols can protect neuronal cells against excitotoxicity, the exact mechanism remains unclear. Studies have shown that some of these compounds protect neurons by reducing glutamate-mediated Ca2+ influx inhibiting Protein Kinase C activity and the subsequent phosphorylation of NR1 of the N-methyl-d-aspartate (NMDA) receptor (NMDAR) [13]

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