Evaluation of the Combined Therapeutic Potential of Turmeric and Donepezil on the Cholinergic System in a Mouse Model of AD-like Pathology

Introduction: The multifactorial pathogenesis of Alzheimer’s Disease (AD) makes effective prevention and treatment challenging. Integrative medicine presents a promising approach by complementing conventional treatments with neuroprotective nutraceuticals. This study investigates the individual and combinatorial effects of turmeric, a neuroprotective herb, and donepezil, an acetylcholinesterase (AChE) inhibitor, on cognitive functions in a scopolamine-induced amnesic mouse model. Methods: Molecular interactions of curcuminoids and donepezil with AChE were analyzed using AutoDock Vina and AMBER22. In animal model studies, amnesia was induced in BALB/c mice via subcutaneous injections of scopolamine (1mg/kg/day) for a duration of 25 days. From the 11th day onwards, the turmeric rhizome powder (20mg/kg/day) and donepezil (0.5mg/kg/day) were orally administered as monotherapies or in combination. Cognitive functions were assessed through behavior tests. Results: Molecular docking and dynamics simulations revealed that curcuminoids (curcumin, bisdemethoxycurcumin, and desmethoxycurcumin) inhibited AChE more effectively than donepezil. Animal studies demonstrated significant enhancements in spatial, reference, recognition, and contextual fear memories, with both turmeric and donepezil monotherapies, and their combination therapy. No significant differences were observed between monotherapies, and no additive effect was evident in the combination therapy. Discussion: Co-administration of turmeric and donepezil did not yield a significant additive effect on cognitive improvement in scopolamine-induced amnesic mice. Turmeric monotherapy showed cognitive improvements comparable to those of donepezil monotherapy, highlighting its potential as a candidate therapy for donepezil-resistant AD. Conclusion: Turmeric monotherapy improved cognitive performance similarly to donepezil monotherapy in scopolamine-induced amnesic mice. These preliminary findings require further research, including dose optimization and clinical trials, to establish their clinical relevance.