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One of the well-established models for examining neurodegeneration and neurotoxicity is the  Drosophila melanogaster  model of aluminum-induced toxicity. Anti-cholinesterase drugs have been combined with other neuroprotective agents to improve Alzheimer’s disease management, but there is not much information on the combination of anti-cholinesterases with dietary polyphenols to combat memory impairment. Here, we assess how curcumin influences some of the critical therapeutic effects of donepezil (a cholinesterase inhibitor) in AlCl 3 -treated  Drosophila melanogaster . Harwich strain flies were exposed to 40 mM AlCl 3  – alone or in combination with curcumin (1 mg/g) and/or donepezil (12.5 µg/g and 25 µg/g) – for seven days. The flies’ behavioral evaluations (memory index and locomotor performance) were analyzed. Thereafter, the flies were processed into homogenates for the quantification of acetylcholinesterase (AChE), catalase, total thiol, and rate of lipid peroxidation, as well as the mRNA levels of acetylcholinesterase (ACE1) and cnc/NRF2. Results showed that AlCl 3 -treated flies presented impaired memory and increased activities of acetylcholinesterase and lipid peroxidation, while there were decrease in total thiol levels and catalase activity when compared to the control. Also, the expression of ACE1 was significantly increased while that of cnc/NRF2 was significantly decreased. However, combinations of curcumin and donepezil, especially at lower dose of donepezil, significantly improved the memory index and biochemical parameters compared to donepezil alone. Thus, curcumin plus donepezil offers unique therapeutic effects during memory impairment in the  D. melanogaster  model of neurotoxicity.

drug and chemical toxicology

Curcumin improves the ability of donepezil to ameliorate memory impairment in  Drosophila melanogaster : involvement of cholinergic and cnc/Nrf2-redox systems