Cytoprotective effects of myristicin against hypoxia-induced apoptosis and endoplasmic reticulum stress in rat dorsal root ganglion neurons

The aim of the present study was to investigate the role of myristicin (Myr; 1-allyl-5-methoxy-3,4-methy-lenedioxybenzene), an active aromatic compound isolated from nutmeg, carrot, basil, cinnamon and parsley, in hypoxia-induced apoptosis in rat dorsal root ganglion (DRG) neurons. It was observed that Myr significantly enhanced cell viability in hypoxia-induced DRG neurons in a dose-dependent manner; the optimal concentration of Myr was 50 mu M. Furthermore, Myr reduced the percentage of deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive neuronal cells and influenced the expression of the pro-apoptotic gene B-cell lymphoma 2 (Bcl-2) associated X protein, the apoptosis protease cleaved caspase-3 and the anti-apoptotic gene Bcl-2, in the hypoxia-induced group. In addition, Myr protected against hypoxic injury in DRG neurons by inhibiting malondialdehyde and lactate dehydrogenase, however upregulating superoxide dismutase and glutathione peroxidase. Myr reduced the expression of endoplasmic reticulum stress (ERS) markers, including CCAAT/enhancer-binding protein-homologous protein, glucose-related protein 78 and cleaved caspase-12 in the hypoxia-induced group. To the best of our knowledge, this is the first demonstration of the activity of Myr against hypoxia-induced apoptosis in rat DRG neurons via inhibition of the ERS pathway.