Wedelolactone mitigates mitochondrial dysfunction to enhance food-related biochemical interventions in disc degeneration

Intervertebral disc degeneration (IVDD), a prevalent age-related musculoskeletal disorder, poses a significant global health burden. While understanding that its pathogenesis and identifying its effective therapeutic compounds remain essential, increasing attention has been directed toward bioactive compounds derived from food sources for their potential role in health management. Wedelolactone, a phytochemical with diverse biological activities, has emerged as a promising candidate. This study examines its effects in an IVDD cell model, where nucleus pulposus (NP) cells isolated from Sprague Dawley rat intervertebral discs were exposed to 200 μM H2O2 for 24 hours to induce oxidative stress. Wedelolactone significantly reduced H2O2-induced reactive oxygen species (ROS) production and alleviated mitochondrial dysfunction in NP cells. It also inhibited cellular senescence and apoptosis while regulating the expression of genes involved in extracellular matrix synthesis and degradation. Mechanistic investigations revealed that Wedelolactone exerted its protective effects through the AMPK/SIRT1/ PGC1α (adenosine monophosphate-activated protein kinase/silent information regulator 1/peroxisome prolifera-tor-activated receptor coactivator-1 alpha) axis, highlighting its role in mitochondrial homeostasis. These findings suggest that Wedelolactone, a potential food-derived compound, could be a promising candidate for functional food development aimed at mitigating IVDD and associated mitochondrial dysfunction.