Food-derived phenolics from Sorghum bicolor modulate NRF2-mediated redox homeostasis in auditory sensory neurons

Oxidative stress–induced cellular injury is a key mechanism underlying tissue dysfunction, and food-derived phenolic compounds have attracted interest as natural modulators of redox homeostasis. Sensory cells, including auditory-derived cells, are particularly vulnerable to oxidative stress and provide a sensitive model for evaluating cytoprotective food bioactives. This study investigated the antioxidant and cytoprotective effects of Sorghum bicolor (SB) extract and its major phenolic constituent, protocatechuic acid (PCA), focusing on NRF2-associtated redox regulation. Oral administration of SB extract attenuated oxidative damage and preserved tissue integrity in an oxidative stress–sensitive murine model. Complementary in vitro and ex vivo analyses using auditory-derived cells and cochlear explants demonstrated that SB reduced reactive oxygen species accumulation, restored cell viability, and mitigated transcriptomic dysregulation associated with apoptosis and mitochondrial dysfunction. SB treatment activated the NRF2/HO-1 pathway and upregulation of downstream antioxidant enzymes. PCA reproduced these antioxidant and anti-apoptotic effects and showed predicted structural compatibility with KEAP1. These findings support Sorghum bicolor as a functional food–derived bioactive resource enhancing redox resilience in sensory cells under oxidative stress conditions. • Sorghum bicolor extract enhances cellular redox homeostasis under oxidative stress conditions. • Food-derived phenolics from sorghum activate NRF2-dependent antioxidant signaling pathways. • Protocatechuic acid is identified as a major phenolic contributor to NRF2-associated cytoprotection. • Sorghum-derived bioactives reduce oxidative stress–induced apoptosis in sensory-derived cell models. • Oral administration of Sorghum bicolor extract preserves tissue integrity in an oxidative stress–sensitive in vivo model.