Ferulic acid protects PC12 neurons against hypoxia by inhibiting the p-MAPKs and COX-2 pathways

OBJECTIVE(S): Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. Here, the protective effects of ferulic acid (FA) on hypoxia-induced neurotoxicity in PC12 cells were evaluated. MATERIALS AND METHODS: We investigated the effect of FA on PC12 cells subjected to hypoxia stress, in vitro. RESULTS: FA increased cell viability, prevented membrane damage (LDH release), scavenged free radicals, increased superoxide dismutase (SOD) activity, and attenuated the elevation of intracellular free Ca(2+), lipid peroxidation, apoptosis (evaluated by TUNEL staining) and PGE(2) production in hypoxia-stressed PC12 cells. MAPKs were activated during hypoxia. FA reduced p-p38 MAPK, caspase-3, and COX-2 activation which correlated well with diminished LDH release in PC12 cells under hypoxia. Furthermore, FA reduced lipid peroxidation in PC12 cells subjected to hypoxia. CONCLUSION: Taken together, these results indicate that FA antioxidant effects could partly be involved in inhibition of p38 MAPK pathway and apoptosis through scavenging ROS in hypoxia-stressed PC12 cells.