What they found

TL;DR (qwen3.6:35b): Sanghuangporus sanghuang extract protects cochlear hair cells from oxidative stress and acoustic trauma by activating the Nrf2/HO-1 antioxidant pathway. This fungal-derived treatment preserved hair cell structure and hearing function in cellular, ex vivo, and mouse models.

Noise-induced hearing loss (NIHL) is a major form of sensorineural hearing impairment driven by oxidative stress-mediated cochlear injury. Sanghuangporus sanghuang (SS), a medicinal fungus extensively studied in microbiology and biotechnology, is known to produce bioactive metabolites with antioxidant properties; however, its functional role in the auditory system has not been established. This study investigated the otoprotective potential of SS extract against oxidative and acoustic stress using complementary in vitro, ex vivo, and in vivo models. In H2O2-treated UB-OC1 auditory cells, SS (25-200 μg/mL) dose-dependently restored cell viability and significantly reduced intracellular reactive oxygen species accumulation. Western blot analysis demonstrated that SS suppressed the expression of apoptotic markers, including cleaved caspase-3 and cytochrome C. At the molecular level, SS upregulated Nrf2 and HO-1 expression at both mRNA and protein levels, without a significant change in Keap1 expression, indicating activation of endogenous antioxidant defense via the Nrf2/HO-1 signaling axis. Consequently, downstream antioxidant genes such as SOD1 and NQO1 were significantly upregulated. In ex vivo cochlear explant cultures, SS preserved hair cell integrity against H2O2-induced damage, as confirmed by phalloidin staining. In a murine NIHL model, oral administration of SS attenuated ABR threshold shifts, maintained Wave I amplitudes, and preserved the structural organization of outer hair cells across all cochlear turns. Collectively, these findings demonstrate that SS confers otoprotection by modulating the Nrf2/HO-1 antioxidant axis and mitigating oxidative stress-induced sensory cell injury, supporting the potential of SS as a fungal-derived functional bioactive resource for redox-associated cochlear protection.

How this applies to our program

This research highlights a potential pharmacological strategy to mitigate oxidative damage in sensory cells, which is relevant to understanding secondary injury mechanisms in STRC/DFNB16-related pathologies. While targeting a different gene, the Nrf2/HO-1 axis offers insights into preserving hair cell viability against stressors that may exacerbate genetic hearing loss.

Key numbers

  • SS extract concentrations of 25-200 μg/mL were used to restore cell viability in vitro
  • Nrf2 and HO-1 expression was upregulated at both mRNA and protein levels
  • Oral administration preserved outer hair cell structural organization across all cochlear turns in mice

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