Evaluation of potential neuroprotective effects of Vanillin against MPP+/MPTP-induced dysregulation of dopaminergic regulatory mechanisms in SH-SY5Y cells and a mouse model of Parkinson's disease

Abstract Parkinson's disease (PD) is the second most progressive neurodegenerative disease, secondarily to Alzheimer's disease. The pathogenesis of PD is still unknown and drugs available for PD treatment either have side effects or suboptimal efficacy. Flavonoids are potent antioxidants with little toxicity with extended use, suggesting they might hold promising therapeutic potential against PD. Vanillin (Van) is a phenolic compound that has exhibited neuroprotective properties in various neurological disorders, including PD. However, the neuroprotective role of Van in PD and its underlying mechanisms are scarce therefore need more exploration. Here, we evaluated the neuroprotective potential of Van and its associated mechanisms against MPP+/MPTP-induced dopaminergic neuronal loss in differentiated human neuroblastoma (SH-SY5Y) cells and mice model of PD. In the present study, Van treatment significantly increased cell viability, reduced oxidative stress, mitochondrial membrane potential and apoptosis in MPP+-intoxicated SH-SY5Y cells. Moreover, Van significantly attenuated the effects of MPP+ on the tyrosine hydroxylase (TH) protein expression and mRNA expressions of GSK-3β, PARP1, p53, Bcl-2, Bax and Caspase-3 genes in SH-SY5Y cells. Similar to our in vitro results, Van provided significant neuroprotection against MPTP-induced neurobehavioral deficits, oxidative stress, aberrant TH protein expressions and immunoreactivity in SNpc of mice brains. Treatment of Van also prevented MPTP-induced loss of dopaminergic TH-positive neurons in SNpc and TH-fibers projecting to the striatum of mice. Thus, Van exhibited promising neuroprotective properties in the current study against MPP+/MPTP-intoxicated SH-SY5Y cells and mice, indicating its novel therapeutic potential against PD.