Tangeretin inhibits ferroptosis through the Nrf2/GPX4 pathway and promotes functional recovery in mice with spinal cord injury.

Abstract

BACKGROUND: Tangeretin (TAN) has antioxidant and anti-inflammatory characteristics. This study aims to investigate its effects on neurological recovery following spinal cord injury (SCI). METHODS: A mouse SCI model and a lipopolysaccharide (LPS)-induced BV-2 cell model were constructed. BV-2 cell proliferation was evaluated by CCK-8 assay and EdU staining. LDH kit and flow cytometry were used to detect BV-2 cell damage, different kits to detect ferroptosis-related indicators. Histopathological damage was observed by pathological staining. The Nrf2/GPX4 pathway and ferroptosis-related proteins were examined using Western blot. RESULTS: TAN treatment attenuated LPS-induced BV-2 cell injury while reduced lipid peroxidation and ROS content. TAN improved behavioural scores, attenuated histopathological damage, and promoted neurofilament regeneration in SCI mice. Notably, TAN reduced mitochondrial damage and ferroptosis in SCI model, activated the Nrf2/GPX4 pathway, whereas Nrf2 inhibitor attenuated the protective effect of TAN. CONCLUSION: TAN inhibits ferroptosis in SCI model through activating Nrf2/GPX4 pathway.