Hydroxytyrosol Attenuates Reserpine-Induced Parkinsonism and Hippocampal Damage by Downregulating Pro-inflammatory...

Parkinson's disease (PD) is a common neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra, resulting in motor and non-motor symptoms. Neuroinflammation in the hippocampus and the potential transcriptional dysregulation of the MAPK/AP-1-Related Gene are key mechanisms involved in cognitive deficits associated with PD. This study examined the anti-inflammatory, antioxidant, and potential neuroprotective properties of hydroxytyrosol (HT) in a reserpine-induced rat model of Parkinsonian-like symptoms. Male Wistar rats were divided into five groups: control, vehicle + saline (VR + NS), RES + NS, HT + VR, and RES + HT. Behavioral assessments, including catalepsy, rotarod, beam walking, Y-maze, and passive avoidance tests, were conducted to evaluate motor and cognitive functions. Additionally, oxidative stress biomarkers, pro-inflammatory cytokines, acetylcholinesterase (AChE) activity, the mRNA expression levels of MAPK8, JUN and FOS, and the density of dark neurons in the hippocampus were measured. HT administration significantly enhanced motor and cognitive performance, lowered oxidative stress markers, regulated cytokine levels, reduced the mRNA expression of MAPK8, JUN and FOS, and reduced hippocampal dark neuron density. These findings suggest that HT's effects against RES-induced neuronal injury are associated with transcriptional downregulation of these genes, supporting its potential as a supportive approach to mitigate inflammation and preserve cognitive function in this Parkinsonian-like model. It should be noted that only mRNA levels were assessed; functional pathway activation via phosphorylation was not evaluated.