Black mulberry (Morus nigra L.) is a common edible fruit from the Moraceae family with a wide variety of nutritional and medicinal applications, mainly due to its antioxidant and anti-inflammatory properties. The purpose of this work was to investigate the cytoprotective and neuroprotective capacity of a hydrophilic black mulberry solvent-free extract rich in polyphenols, including the antioxidant, antiradical, and enzymatic mechanisms that would explain these effects. Its neuroprotective potential was evaluated in vitro using the Neuro-2a cell line and in vivo through the Caenorhabditis elegans organism model. Neuro-2a cells were treated at different concentrations of the extract (25-500 µg/mL) and hydrogen peroxide (300 µM) as an oxidant agent, simultaneously. From these treatments, redox status (intracellular ROS production) and cellular activity (MTT) were also quantified in Neuro-2a. Regarding the C. elegans assay, the protection of the extract against β-amyloid toxicity was measured against the CL4176 strain, which is a model of Alzheimer disease. As a complementary neuroprotective assay, its potential to inhibit the monoamine oxidase A (MAO-A) enzyme was measured. In addition, an Artemia salina bioassay was performed for preliminary toxicity screening. And its antioxidant properties were evaluated by means of the FRAP assay. The results confirm its neuroprotective potential and its ability to scavenge free radicals and decrease ROS production, also acting as a moderate MAO-A inhibitor. Moreover, the polyphenolic extract alleviates the toxicity induced by β-amyloid accumulation in C. elegans. Concluding, Morus nigra can be considered a functional food with bioactive compounds that may prevent the onset of neurodegenerative diseases.
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