Neuroprotective effect of Carnosic acid in Rotenone induced Parkinson’s disease in mice
Abstract
Background/Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress and mitochondrial dysfunction. Current therapies mainly provide symptomatic relief without preventing disease progression. Carnosic acid (CA), a natural phenolic diterpene from Rosmarinus officinalis, possesses antioxidant and anti-inflammatory properties with potential neuroprotective effects. This study evaluated the neuroprotective effects of CA, alone and combined with levodopa, in a rotenone-induced mouse model of Parkinson’s disease. Methodology: Forty-two adult male Swiss albino mice were randomly assigned to seven groups (n=6/group): control, rotenone, CA 20 mg/kg, CA 40 mg/kg, CA 20 mg/kg + levodopa, CA 40 mg/kg + levodopa and levodopa alone. Parkinsonism was induced with rotenone (2.5 mg/kg, intraperitoneally) for 21 days. Serum triiodothyronine, nitric oxide, lipoxygenase, total antioxidant capacity, and superoxide dismutase were estimated. Anxiety-like behavior was assessed using the Elevated Plus Maze and Open Field Test. Data were analyzed using one-way ANOVA with Bonferroni post-hoc test. Results: Rotenone reduced serum T3, TAC, and SOD while increasing NO and LPX levels, indicating oxidative stress. It also induced anxiety-like behaviour. CA treatment dose-dependently improved biochemical and behavioural changes, with CA 40 mg/kg +levodopa producing near-normal antioxidant status, reduced oxidative stress markers, restored T3 levels, and the greatest improvement in behavioral performance. Conclusion: Carnosic acid exerted significant neuroprotective effects against rotenone-induced Parkinsonism by restoring antioxidant defenses, reducing oxidative stress, normalizing thyroid hormone levels, and improving anxiety behaviour. Combined therapy with levodopa showed superior benefits, suggesting CA as a promising adjunctive treatment targeting multiple pathogenic mechanisms in Parkinson’s disease.