The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson’s Disease

Parkinson’s disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physiopathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5⁺, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5⁺ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5⁺ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5⁺ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect.