Inhibitory effect of ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on memory impairment and neuronal toxicity induced by beta-amyloid.

The components of the herb Magnolia officinalis have exhibited antioxidant and neuroprotective activities. In this study, we investigated effects of ethanol extract of M.officinalis and its major component 4-O-methylhonokiol on memory dysfunction and neuronal cell damages caused by A beta. Oral pretreatment of ethanol extract of M. officinalis (2.5, 5 and 10mg/kg) and 4-O-methylhonokiol (1mg/kg) into drinking water for 5 weeks suppressed the intraventricular treatment of A beta(1-42) (0.5 microg/mouse, i.c.v.)-induced memory impairments. In addition, 4-O-methylhonokiol prevented the A beta(1-42)-induced apoptotic cell death as well as beta-secretase expression. 4-O-methylhonokiol also inhibited H(2)O(2) and A beta(1-42)-induced neurotoxicity in cultured neurons as well as PC12 cells by prevention of the reactive oxygen species generation. 4-O-methylhonokiol also directly inhibited beta-secretase activity and A beta fibrilization in vitro. Thus, ethanol extract of M. officinalis may be useful for prevention of the development or progression of AD, and 4-O-methylhonokiol may be a major active component.