• Daphnetin attenuates TBHP-induced ECM degradation, oxidative stress, and NLRP3 inflammasome activation in nucleus pulposus cells.
• Daphnetin facilitates mitophagy to remove damaged mitochondria, reducing mitochondrial ROS and alleviating NLRP3 inflammasome activation.
• The protective effect of Daphnetin is mediated via the Nrf2/PINK1 signaling pathway.
• In vivo, Daphnetin prevents intervertebral disc degeneration in a rat puncture model, suggesting its therapeutic potential.