(290) Exploring the Therapeutic Potential of Blueberry-Derived Exosomes in Neurodegenerative Disease Management

Objective : Blueberries are known for their health benefits against neurodegenerative diseases by reducing oxidative stress and enhancing cognitive function. This study investigates the potential of blueberry-derived exosomes (BBDExo) as a natural nanosized antioxidant system for treating neurodegenerative diseases.

Methods: Nanosized BBDExo were isolated from blueberries using sequential centrifugation and characterized for protein and polyphenol contents. The stability of BBDExo under gastrointestinal conditions was assessed. The uptake of BBDExo by brain endothelial bEND.3 cells and their effects on neuronal SH-SY5Y cells were evaluated to determine potential therapeutic impacts. Dopaminergic-specific behaviors were used to assess the efficacy of exosomes in repairing neuronal damage in a methylmercury-treated Caenorhabditis elegans Parkinson's disease model.

Results: BBDExo exhibited nanosized, oval-shaped morphology with an average size of 82.7±6.4 nm. BBDExo demonstrated stability in simulated gastrointestinal environments, protecting the polyphenol contents for 4 hours. The cellular uptake of BBDExo increased in a dose-dependent manner in brain endothelial bEND.3 cells, suggesting possible transport across the blood-brain barrier. BBDExo significantly promoted the proliferation of SH-SY5Y neuronal cells, with a maximal increase of 158.8±1.8% at a concentration of 25 µg/mL. BBDExo significantly reduced the release of the pro-inflammatory cytokine interleukin-8 in stressed SH-SY5Y cells. Exosome treatment significantly improved dopaminergic function in C. elegans compared to the phosphate-buffered saline (PBS) control group, even approaching the function of those without neuronal damage.

Conclusions: BBDExo demonstrates potential as a novel nanomedicine for neurodegenerative diseases, offering a dual mechanism of action by protecting bioactive compounds during delivery and repairing neurological behavior. They may offer a promising approach for enhancing therapeutic efficacy and disease management.