Astaxanthin nanoemulsion attenuates paraquat-induced Parkinsonism via modulation of oxidative stress, neuroinflammation, and dopaminergic dysfunction in rats

1. BACKGROUND: 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. 2. METHODS: 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. 3. RESULTS: 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. 4. CONCLUSION: 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.