Tetrahydrocurcumin exhibits neuroprotective effects by inhibiting neuron ferroptosis via activity of iPLA2β/p38 MAPK phosphorylation in rat TBI model.

Abstract

Ferroptosis characterized by iron-dependent lipid peroxidation induced by traumatic brain injury (TBI) is an important factor that aggravates diseases. Studies have shown that tetrahydrocurcumin (THC) has neuroprotective effects in brain injury. However, whether THC inhibits neurocyte ferroptosis after TBI and its mechanism remains unclear. To investigate this, a weight-drop model in rats and H₂O₂ induced oxidative stress model in SH-SY5Y cells were established, and THC was used for treatment. Immunohistochemical staining showed that iron deposition reached its peak at 8th day after TBI. We found that THC remarkably inhibited iron accumulation in the cortical cortex and corpus callosum, improved neurological damage, reduced acute cerebral edema, weight loss, oxidative stress, and inflammation. Furthermore, the activity of iPLA2β was significantly reduced, and phosphorylation of p38 was increased after TBI, while THC alleviated the decrease in iPLA2β activity and increase in the level of P-p38. It confirmed that THC effectively mitigated ferroptosis, while iPLA2β inhibitor s-BEL could reverse the effects of THC on ferroptosis in vivo and in vitro experiments. In addition, SB202190 which is an inhibitor of p38 could enhance THC protection and lessen formation of ferroptosis-related proteins in cells. In conclusion, these findings suggested that THC may promote neurological function recovery after TBI by inhibiting neuron ferroptosis via activity of iPLA2β/P-p38.