Synergistic effects of curcumin-donepezil therapy in a Drosophila Alzheimer's disease model.

BACKGROUND

Despite emerging therapeutic options, Alzheimer´s disease (AD) management remains suboptimal due to multimodal pathogenesis. We investigated curcumin-donepezil combination therapy, as curcumin demonstrates antioxidant, anti-inflammatory, and anti-amyloidogenic properties that may complement donepezil's cholinesterase inhibition.

RESEARCH DESIGN AND

METHODS

We employed the elav-Gal4/UAS-hAPP-BACE-1 Drosophila melanogaster model alongside molecular docking simulation and ADMET prediction to evaluate curcumin-donepezil combination versus monotherapy. Fruit flies received the treatment regimen, and were tested for survival, memory performance, and biochemical markers, including BACE-1 activity and oxidative stress parameters.

RESULTS

Combination therapy significantly improved survival rates and memory performance compared to individual treatment. The combination effectively modulated multiple AD-related pathways, demonstrating reduced BACE-1 activity and decreased oxidative stress markers. Molecular docking confirmed favorable drug interactions, and ADMET profiles supported therapeutic viability.

CONCLUSIONS

Curcumin-donepezil combination therapy shows promise as a multi-target approach for AD management. However, translation to clinical applications requires validation in higher-order models and human trials.