Neuroprotective effects of nootkatone from Alpiniae oxyphyllae Fructus against amyloid-β-induced cognitive impairment.

The sesquiterpene nootkatone (NKT), isolated from Alpiniae oxyphyllae Fructus, was shown to possess protective effects on neurons. In our study, by using an Alzheimer's disease (AD) model of mice induced by intracerebroventricular (i.c.v.) injection of Aβ1-42 oligomers, we investigated the effects of NKT on memory impairment and further evaluated the pathological changes of mice. AD mice were treated by i.c.v. injection of NKT (at a dose of 0.02 mg/kg and 0.20 mg/kg) or vehicle (PBS) into the lateral ventricle once daily for 5 consecutive days. The behavioral tasks were performed, and levels of some biochemical indicators and histopathological changes of the brain were evaluated to elucidate the mechanism of NKT in the treatment of AD. The results revealed that NKT significantly improved the neurobehavioral performance of the AD mice in the Y-maze and Morris water maze tests. More importantly, NKT treatment decreased the malondialdehyde (MDA), Aβ as well as the acetylcholin esterase (AChE) levels in the mice brain, while increased the glutathione peroxidase (GSH-Px) levels with improved histopathological changes in the hippocampus. These findings provided evidences for the beneficial role of NKT in Aβ1-42-induced mice AD model linking to anti-oxidative and anti-AChE activities with inhibitory effect against Aβ accumulation.