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

Abstract

<em>Objective(s):</em>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. <br/><em>Materials and Methods:</em>We investigated the effect of FA on PC12 cells subjected to hypoxia stress,<em> in vitro</em>. <br/><em>Results:</em>FA increased cell viability, prevented membrane damage (LDH release), scavenged free radicals, increased <em>s</em><em>uperoxide</em> dismutase (SOD) activity, and attenuated the elevation of intracellular free Ca²⁺, lipid peroxidation, apoptosis (evaluated by TUNEL staining) and PGE₂ 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. <br/><em>Conclusion:</em>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.