In-vitro neuroprotective effect and mechanism of 2-hydroxy--cadinol against amyloid -induced neuronal apoptosis

Amyloid beta (A beta) neurotoxicity plays a causative role in the pathogenesis of Alzheimer's disease. Accumulating evidence demonstrates that A beta neurotoxicity is mediated by glutamate excitotoxicity. In our previous study, a sesquiterpenoid compound 2 beta-hydroxy-delta-cadinol (HOC) which exhibited antiglutamate excitotoxicity effect was isolated from the fruits of Alpinia oxyphylla Miquel. Based on the antiglutamate excitotoxicity effect of HOC, in this study, we investigated the potential benefit of HOC in preventing A beta((1-42))-induced neuronal apoptosis in cultured rat hippocampal neurons. The neuroprotective effect of HOC against A beta((1-42))-induced neuronal apoptosis was assessed by Hoechst 33258 staining, reactive oxygen species (ROS) production, caspase-3 activation and caspase-3 activity. Results demonstrated that HOC treatment significantly prevented A beta((1-42))-induced neuronal apoptosis. The underlying molecular mechanisms of HOC in preventing A beta((1-42))-induced neuronal apoptosis may be via inhibiting A beta((1-42))-induced ROS production, attenuating A beta((1-42))-induced caspase-3 activation and inhibiting caspase-3 activity. This study suggests that HOC may be a potential agent for the prevention of A beta neurotoxicity.