Ameliorating effect of Citrus aurantium extracts and nobiletin on β‑amyloid (1‑42)‑induced memory impairment in mice.

The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid β 1‑42 (Aβ 1‑42)‑induced spatial learning and memory impairment in mice. After injecting Aβ 1‑42 (5 µl/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, Bcl‑2, and cleaved caspase‑3 protein expression by western blot assays was used to confirm the anti‑apoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Aβ‑induced 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 caspase‑3 protein expression and upregulated the Bcl‑2 and Bcl‑2/Bax expression in the cortex and hippocampus of Aβ‑treated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating anti‑apoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.