Evaluation of myristica dactyloides seeds extract on rotenone induced dopamine depletion, dopaminergic neurodegeneration and oxidative imbalance in a rat model of PD

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and oxidative stress. The present study investigated the neuroprotective effect of Myristica dactyloides seed extract (MDSE) against rotenone-induced Parkinsonism in rats. Male Wistar rats were divided into six groups and treated with rotenone (2.5 mg/kg, i.p.) alone or in combination with MDSE (5, 10, and 20 mg/kg, p.o.) for 30 days. Neurochemical parameters including dopamine (DA) and its metabolites, oxidative stress markers such as lipid peroxidation (LPO), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) were evaluated. Rotenone administration significantly depleted striatal dopamine levels, increased lipid peroxidation, and reduced antioxidant enzyme activities. Furthermore, rotenone reduced the expression of dopaminergic markers including tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter-2 (VMAT-2). Co-administration of MDSE significantly attenuated rotenone-induced neurochemical and oxidative alterations in a dose-dependent manner. The highest dose of MDSE (20 mg/kg) markedly restored antioxidant status and dopaminergic function. These findings demonstrate that MDSE possesses significant neuroprotective activity against rotenone-induced Parkinsonian neurodegeneration, likely through antioxidant and dopaminergic protective mechanisms.

Keywords: Parkinson’s disease, Myristica dactyloides, Rotenone, Dopamine, Oxidative Stress