Acetylcholinesterase inhibitory activity and neuroprotection in vitro, molecular docking, and improved learning and memory functions of demethylcurcumin in scopolamine-induced amnesia ICR mice
In this study, demethylcurcumin (DC), the minor constituent in curcuminoids, showed better than those of curcumin in anti-acetylcholinesterase (anti-AChE) activities, anti-amyloid β peptide aggregations, neuroprotective activities in 6-hydroxydopamine-treated SH-SY5Y cell models, and anti-nitric oxide productions in lipopolysaccharide-treated RAW 264.7 macrophages. Based on molecular docking analyses with AChE, the meta-hydroxyl group in DC, nonexistent in curcumin, showed the formation of hydrogen bonds with Ser293 and Tyr341 in the binding sites of AChE. For animal experiments, the scopolamine-induced amnesia ICR mice were used to analyze the learning and memory functions of DC in comparisons with positive control of donepezil. Mice fed with DC (50 mg/kg) or donepezil (5 mg/kg) demonstrated to improve and showed a significant difference compared to those in the control group (P < 0.05, 0.01, or 0.001) in a passive avoidance test and in a water maze probe test. The brain extracts of the mice in the DC or donepezil group showed reduced AChE activities and higher ORAC activities and also showed a significant difference compared to those in the control group (P < 0.05, 0.01, or 0.001). DC might be beneficial to develop functional foods or as a lead compound for degenerative disorders.