4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase

Oxidative stress induced neuronal cell death by accumulation of beta-amyloid (A beta) is a critical pathological mechanism of Alzheimer's disease (AD). Intracerebroventrical infusion of A beta(1-42) (300 pmol/day per mouse) for 14 days induced neuronal cell death and memory impairment, but pre-treatment of 4-O-methylhonokiol (4-O-MH), a novel compound extracted from Magnolia officinalis for 3 weeks (0.2, 0.5 and 1.0 mg/kg) prior to the infusion of A beta(1-42) and during the infusion dose dependently improved A beta(1-42)-induced memory impairment and prevented neuronal cell death. Additionally, 4-O-MH reduced A beta(1-42) infusion-induced oxidative damages of protein and lipid but reduced glutathione levels in the cortex and hippocampus. A beta(1-42) infusion-induced activation of astrocytes and p38 mitogenic activated protein (MAP) kinase was also prevented by 4-0-MH in mice brains. In further study using culture cortical neurons, p38 MAP kinase inhibitor abolished the inhibitory effect of 4-O-MH (10 mu M) on the A beta(1-42) (5 mu M)-induced reactive oxidative species generation and neuronal cell death. These results suggest that 4-O-MH might prevent the development and progression of AD through the reduction of oxidative stress and neuronal cell death via inactivation of p38 MAP kinase pathway. (C) 2011 Elsevier Inc. All rights reserved.