Punicalagin inhibits neuron ferroptosis and secondary neuroinflammation to promote spinal cord injury recovery.

Spinal cord injury (SCI) represents a severe type of central nervous system damage, with no effective treatment currently available, partly due to neuronal ferroptosis and subsequent neuroinflammation. Punicalagin, an anti-inflammatory compound extracted from pomegranate peel, has exhibited therapeutic potential for inflammatory diseases. In this study, we present evidence that punicalagin facilitates the recovery of neurological function following SCI by mitigating neuronal ferroptosis. Mechanistically, this effect involves the upregulation of nuclear factor E2-related factor 2 (Nrf2) and the activation of the Nrf2- Solute Carrier Family 7 Member 11 (SLC7A11)- Glutathione Peroxidase 4 (GPX4) signaling pathway. Furthermore, punicalagin aids in the resolution of secondary neuroinflammation by modulating the M1/M2 polarization of microglia, thereby promoting SCI recovery. Collectively, these findings suggest that punicalagin enhances functional recovery after SCI by inhibiting neuronal ferroptosis and reducing microglial M1 polarization. Consequently, punicalagin may represent a promising therapeutic agent for the treatment of spinal cord injury.