The Impacts of Hesperidin on Motor-Cognitive Disorders, Oxidative Damage, and Cholinergic Function in the Hippocampus of a Parkinson's Disease Rat Model

Background: Parkinson's disease (PD) represents a neurodegenerative condition where oxidative stress significantly contributes to its underlying pathology. Antioxidant agents may reduce neuronal degeneration. Objectives: This research explores the impact of hesperidin (HES) on the hippocampus's antioxidant capacity and cholinergic function as well as its effects on memory enhancement and offer neuroprotective benefits in a rat PD model elicited by reserpine (RES). Methods: Forty male Wistar rats were assigned to five experimental groups: The control group, a group receiving HES vehicle (normal saline, NS) combined with RES vehicle (VR + NS), a group treated with RES (0.2 mg/kg for 13 days, intraperitoneally) along with NS (RES + NS), a group administered HES (100 mg/kg for 14 days, orally) plus RES vehicle (HES + VR), and finally the group receiving both RES and HES. Following treatment, assessments for catalepsy and memory were performed. The enzymatic activity within the hippocampus, specifically for catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), was measured employing the ELISA method. Simultaneously, the malondialdehyde (MDA) level was quantified employing the thiobarbituric acid assay, while we evaluated the activity of acetylcholinesterase (AChE) using the Ellman method in the hippocampus. Neuronal density in the hippocampal CA1 and CA3 regions was assessed using stereological techniques. Results: The results indicated a significant decrease in cataleptic behavior, AChE activity, and MDA levels, along with an increase in CAT, SOD, GPx, and neuronal density in both CA1 and CA3 regions, alongside enhancements in working and avoidance memory in the RES + HES group in relation to the RES + NS group. Also, HES inhibited the RES-elicited rise in AChE levels within the hippocampus. Conclusions: Hesperidin enhances the hippocampus's antioxidant function, regulates cholinergic activity, and offers neuroprotection against RES-elicited motor-cognitive impairments.