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

Amyloid beta (Aβ) neurotoxicity plays a causative role in the pathogenesis of Alzheimer's disease. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. In our previous study, a sesquiterpenoid compound 2β-hydroxy-δ-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 Aβ(1-42)-induced neuronal apoptosis in cultured rat hippocampal neurons. The neuroprotective effect of HOC against Aβ(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 Aβ(1-42)-induced neuronal apoptosis. The underlying molecular mechanisms of HOC in preventing Aβ(1-42)-induced neuronal apoptosis may be via inhibiting Aβ(1-42)-induced ROS production, attenuating Aβ(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 Aβ neurotoxicity.