Abstract
Parkinson's disease (PD) involves dopaminergic dysfunction, oxidative stress, and neuroinflammation. This study evaluated an optimized astaxanthin-loaded nanoemulsion (AXTNE) in paraquat-induced experimental Parkinsonism. Male Wistar rats were randomly assigned to nine groups (n = 6). Parkinsonian alterations were induced by paraquat (10 mg/kg, i.p.) twice weekly for 4 weeks. Aqueous astaxanthin (AXT; 30 mg/kg), AXTNE (15 and 30 mg/kg), levodopa + carbidopa (15 + 3.75 mg/kg), and AXTNE-levodopa combinations were administered orally for 28 days. Motor function was assessed using catalepsy, locomotor activity, grip strength, postural instability, and beam-walk tests. Pooled bilateral striatal tissue was analyzed for oxidative stress, inflammatory cytokines, monoaminergic neurotransmitters, and dopaminergic protein markers. Paraquat induced motor deficits, oxidative imbalance, increased inflammatory cytokines, reduced dopamine and noradrenaline, and altered tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), and α-synuclein levels. AXTNE attenuated these alterations and reduced MDA levels measured by TBARS. AXTNE-levodopa combinations produced additional improvements across several endpoints. AXTNE attenuated multiple paraquat-associated Parkinsonian alterations, with generally greater numerical improvements than aqueous AXT. Combination with levodopa showed potential complementary effects. Further histopathological, pharmacokinetic, biodistribution, and mechanistic studies are warranted.