Phillyrin Ameliorates Traumatic Spinal Cord Injury by Inhibiting Inflammation, Oxidative Stress, and Pyroptosis Through Modulation of the Nrf2/HO-1 Signaling Pathway.

Abstract

BACKGROUND: Treating traumatic spinal cord injury (SCI) requires mitigating microglia-mediated inflammation and nerve damage. Phillyrin (phi) shows neuroprotective potential, but its effects on SCI are unknown. We investigated phi's impact on microglial activation, inflammation, neuronal apoptosis, and pyroptosis in mice after SCI. METHODS: A mouse contusion SCI model was used to assess phi efficacy. Functional recovery was assessed with BBB and LSS scales. Histological and TUNEL staining were used to evaluate tissue damage and neuronal survival. Microglial phenotypes, inflammation, pyroptosis, oxidative stress and Nrf2/HO-1 pathway were analyzed. RESULTS: Phi treatment accelerated motor function recovery, improved tissue pathology, increased live cells, and reduced apoptosis. Phi treatment showed a decrease in the proportion of M1 pro-inflammatory microglia characterized by iNOS, an increase in the proportion of M2 anti-inflammatory microglia characterized by Arg1 and a reduction in inflammatory factors. Phi enhanced Nrf2 expression in neurons and microglia, activated HO-1 and NQO1 expression, weaken oxidative stress, and improved pyroptosis. CONCLUSION: Phi alleviates SCI by activating the Nrf2/HO-1 pathway, suppressing microglial activation-mediated neuroinflammation, neuronal apoptosis, oxidative stress and pyroptosis. This study provides the first evidence of the therapeutic effect of phi on traumatic SCI, providing theoretical support for its future clinical application in SCI.