Neuroprotective effects of alpha-mangostin on [MPP.sup.+]-induced apoptotic cell death in neuroblastoma SH-SY5Y cells

In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from [MPP.sup.+]-induced apoptosis. The effects of alpha-mangostin on [MPP.sup.+]-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative realtime PCR for the expression of p53, Bax, and Bcl2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of [MPP.sup.+] on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by [MPP.sup.+]. Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha- mangostin and [MPP.sup.+]. The cotreated cells showed a significant decrease in activated caspase-3 compared with [MPP.sup.+] treatment alone. Our data suggest that cytoprotection of alpha-mangostin against [MPP.sup.+]-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.