Sargassum Thunbergii Extracts Protect Cochlear Hair Cell-like Cells against Oxidative Stress-induced Damage via NRF2/HO-1 Antioxidant Pathway
Hearing loss is a prevalent sensory disorder in which oxidative stress plays a central role in cochlear damage. This study evaluated the cytoprotective and antioxidant effects of Sargassum thunbergii (Mertens ex Roth) Kuntze(ST) extracts in UB-OC1 cells and investigated the underlying molecular mechanisms. Among the fractions, the water extract (STW) and celluclast-assisted extract (STC) showed low cytotoxicity and significantly attenuated H2O2-induced cell damage, whereas the other fractions showed higher toxicity. STW and STC effectively reduced the intracellular reactive oxygen species (ROS) levels in a dose-dependent manner, indicating direct antioxidant activity. Mechanistically, STW and STC enhanced NRF2 activation, as evidenced by the increased intracellular accumulation and nuclear localization of NRF2. Although Nrf2 mRNA expression showed only modest changes, the downstream target gene HO-1 was significantly upregulated, while keap1 expression was reduced, suggesting enhanced NRF2 stabilization and activation. These findings show that STW and STC protect cochlear hair cell-like cells against oxidative stress-induced damage by suppressing ROS accumulation and activating the NRF2/HO-1 signaling pathway. These results suggest that S. thunbergii may be a promising functional resource for protecting auditory hair cell-like cells against oxidative stress.