Ferulic acid protects PC۱۲ neurons against hypoxia by inhibiting the p-MAPKs and COX-۲ 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 PC۱۲ cells were evaluated. Materials and Methods:We investigated the effect of FA on PC۱۲ 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 Ca۲+, lipid peroxidation, apoptosis (evaluated by TUNEL staining) and PGE۲ production in hypoxia-stressed PC۱۲ cells. MAPKs were activated during hypoxia. FA reduced p-p۳۸ MAPK, caspase-۳, and COX-۲ activation which correlated well with diminished LDH release in PC۱۲ cells under hypoxia. Furthermore, FA reduced lipid peroxidation in PC۱۲ cells subjected to hypoxia. Conclusion:Taken together, these results indicate that FA antioxidant effects could partly be involved in inhibition of p۳۸ MAPK pathway and apoptosis through scavenging ROS in hypoxia-stressed PC۱۲ cells.

Keywords:

Caspase-۳ , Ferulic acid , Hypoxia , MAPKs , ROS