Extract from Nasco pomace loaded in nutriosomes exerts anti-inflammatory effects in the MPTP mouse model of Parkinson's disease

: Neuroinflammation has recently emerged as a key event in Parkinson's disease (PD) pathophysiology and as a potential target for disease-modifying therapies. Plant-derived extracts, rich in bioactive phytochemicals with antioxidant properties, have shown potential in this regard. Yet their clinical utility is hampered by poor systemic availability and rapid metabolism. Recently, our group demonstrated that intragastric delivery of Nasco pomace extract via nutriosomes (NN), a novel nanoliposome formulation, contrasts the degeneration of nigrostriatal dopaminergic neurons in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In the present study, we investigated the impact of intragastric NN treatment on the reactivity of glial cells in the substantia nigra pars compacta (SNc) and caudate-putamen (CPu) of MPTP-treated mice. To this scope, in mice exposed to MPTP (20 mg/kg/day, × 4 days), we conducted immunohistochemistry analyses of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) to assess the responsiveness of astrocytes and microglial cells, respectively. Additionally, we studied the co-localization of the pro-inflammatory interleukin (IL)-1β and tumor necrosis factor (TNF)-α with IBA1 to obtain insights into microglial phenotype. Immunohistochemical results showed that NN administration significantly mitigated astrogliosis and microgliosis in the CPu and SNc of mice receiving subacute MPTP treatment, with region-specific variations in anti-inflammatory efficacy. Remarkably, the CPu showed a heightened response to NN treatment, including a pronounced decrease in microglial IL-1β and TNF-α production. Altogether, these findings underscore the anti-inflammatory effects of NN treatment and provide a potential mechanism underlying the neuroprotective effects previously observed in a subacute MPTP mouse model of PD.