Co-Administration of Luteolin and Curcumin: Neuroprotective and Antioxidant Potential in Parkinson’s Disease Using Drosophila melanogaster Model

Abstract

Parkinson's disease (PD), a progressive neurodegenerative disorder, is marked by dopaminergic neuronal loss in the substantia nigra and the pathological accumulation of alpha-synuclein. Current treatments primarily address symptoms without halting disease progression, underscoring the need for novel therapeutic strategies. This study investigated the effects of co-administration of luteolin and curcumin in a transgenic Drosophila melanogaster model of PD. Luteolin and curcumin, recognized for their antioxidant and anti-inflammatory properties, were administered to evaluate their impact on survival rates, locomotory activity, muscular integrity, and oxidative stress markers. Results demonstrated that the treated group exhibited a significant increase in survival rate and improved locomotory and exploratory activities compared to untreated mutants. The larva crawling assay revealed enhanced muscular integrity, suggesting the restoration of motor function. Biochemical assays indicated reduced malondialdehyde (MDA) levels and increased catalase and thiol activity in the treated group, highlighting the compounds' ability to mitigate oxidative stress. Molecular docking analyses revealed strong interactions between luteolin, curcumin, and key PD-related proteins, including PERK, AChE, and MAPK10, with high binding affinities and favorable binding free energy values. These findings suggest that luteolin and curcumin target pathways implicated in oxidative stress, neuroinflammation, and protein misfolding, offering a multi-targeted approach to PD therapy. This study underscores the therapeutic potential of luteolin and curcumin as complementary agents in managing Parkinson’s disease, paving the way for further exploration into their clinical applicability.