Ameliorative potential of coumaric acid and imeglimin against reserpine-induced parkinsonism in rats

Background: Parkinson’s disease involves dopaminergic degeneration, oxidative stress, and α-synuclein aggregation. Reserpine-induced Parkinsonism mimics these deficits via VMAT-2 inhibition. Coumaric acid and imeglimin possess antioxidant and mitochondrial-protective actions. This study evaluated the individual and combined efficacy of these agents in reducing reserpine-induced behavioural and neurochemical impairments in rats. Methodology: PD was induced in rats by giving reserpine (1 mg/kg, s.c) alternately for three days. Pretreatment with coumaric acid (80 and 100 mg/kg, p.o.), imeglimin (100 & 200 mg/kg, p.o.), and their combination were administered for 5 days. Behavioral assessments (orofacial dyskinesia, H & B test, and rotarod) were performed on day 5, followed by biochemical oxidative stress parameters (CAT, GSH, SOD, and LPO), neurotransmitters (dopamine), and α-synuclein expression with histopathological evaluations. Results: Reserpine-treated rats exhibited pronounced orofacial dyskinesia, reduced motor coordination, dopamine depletion, elevated oxidative stress, and α-synuclein expression. Pretreatment with coumaric acid and imeglimin improved behavioral outcomes, restored antioxidant enzymes, reduced inflammation, and elevated dopamine levels. Combination therapy produced the greatest improvement. Discussion: The combined effects of coumaric acid and imeglimin likely counteract reserpine-induced dopaminergic toxicity through antioxidant enhancement and inhibition of α-synuclein expression. Conclusion: Coumaric acid and imeglimin combination therapy significantly mitigates reserpine-induced Parkinsonism by improving general neuronal integrity and brain function.