Lee_2019_Mol.Med.Rep_20_3448

The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid beta 142 (Abeta 142)induced spatial learning and memory impairment in mice. After injecting Abeta 142 (5 microl/2.5 min, intracerebroventricular injection), amnesic mice were orally administered CAE and nobiletin for 28 days. Memory, spatial and cognitive ability were measured using passive avoidance and a Morris water maze task. Acetylcholinesterase (AchE) activity was investigated in the hippocampus and cortex using commercial kits and the analysis of Bax, Bcl2, and cleaved caspase3 protein expression by western blot assays was used to confirm the antiapoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Abetainduced neurodegenerative mice with increased AchE activity in the brain. However, the daily administration of CAE and nobiletin reduced the spatial learning deficits and increased the AchE activity in the cortex and hippocampus. Furthermore, CAE and nobiletin significantly downregulated the Bax and cleaved caspase3 protein expression and upregulated the Bcl2 and Bcl2/Bax expression in the cortex and hippocampus of Abetatreated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating antiapoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.