DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice

Abstract

Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer’s disease.

Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

“…Our previous studies affirmed the efficacy and safety of DL0410 [ 18 , 19 , 20 , 21 ]. It was observable that DL0410 had the ability to enhance deficits of memory in scopolamine-induced amnesia in mice by increasing the ACh level in a dose-dependent manner [ 20 ]. In addition, DL0410 had an effect on the reduction of Aβ plaques.…”

The effects and mechanisms of the action of galangin on spatial memory in rats

“…In addition, based on the studies reporting the potent acetylcholinesterase inhibitory effect of galangin, it was suggested that galangin might be a potential treatment option in Alzheimer's disease and other dementias (17,23,26,27). Low brain acetylcholine concentrations, especially in the hippocampus, are associated with cognitive dysfunction and increasing acetylcholine concentrations in the brain via inhibition of acetylcholinesterase, which is accepted as a helpful way of treating the cognitive dysfunction seen in Alzheimer's disease and other dementias (28,29). In this study, galangin prevented the memory impairment induced by scopolamine or mecamylamine.…”

Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice

“…In this study, we found that BSYZ could improve the learning and memory of SAMP8 mice, which is according with our previous studies [ 9 , 10 ]. Donepezil (DON) showed the similar effect on elevating the availability of ACh in the brain, which has been documented as critical for the effective management of Alzheimer's disease and used as a positive control in ameliorating memory and cognitive impairments [ 29 , 30 ].…”