Curcumin and curcumin-loaded poly(caprolactone) nanoparticles restore mitochondrial function in an in vitro Parkinson’s disease model

Abstract

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms resulting from the selective loss of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction is a key mechanism in idiopathic and familial PD, yet the cause is poorly understood. Paraquat (PQ) induces mitochondrial dysfunction, though its effect remains uncertain. Curcumin, a phytochemical with antioxidant, antiinflammatory, and neuroprotective properties, shows therapeutic promise for PD but has unfavorable pharmacokinetics. Nanoparticles (NPs) offer a solution by improving curcumin’s stability, bioavailability, and in providing targeted delivery. Purpose: To examine mitochondrial bioenergetics in a PQ-induced PD in vitro model and evaluate the potential of curcumin-loaded polymeric nanoparticles (CNPs) to rescue mitochondrial function. Methods: CNPs were synthesized and characterized to explore therapeutic suitability. Using the Oroboros system, mitochondrial respiration was assessed in SH-SY5Y cells treated with PQ, curcumin, CNPs, and their respective pre- and post-PQ treatment regimens. Furthermore, mitochondrial morphology was assessed. Results: PQ caused a significant decrease in complex I-linked oxidative phosphorylation and the electron transfer system capacity. CNP pre- and post-PQ treatments reduced PQ-induced structural mitochondrial damage. For post-PQ treatment, CNP improved complex IV activity, while curcumin recovered PQ’s effect on N- and Gppathway activity. CNP pre-PQ treatment enhanced pyruvate-linked respiration and reduced ROX levels. Notably, curcumin pre-PQ treatment had the strongest protective effect, restoring multiple respiratory parameters. Conclusion: The findings from this study suggest that curcumin and CNPs have potential in protecting PQ-induced reduction of respiratory states and rates in mitochondria. The findings lay a foundation for optimizing curcumin delivery using NPs for potential therapeutic applications in PD.