Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models. Zebrafish with neomycin-induced ototoxicity were treated with CAE, resulting in otic hair cell protection with an EC₅₀ of 0.49 µg/mL and a therapeutic index of 1020. CAE treatment improved auditory function and protected cochlear sensory cells in a mouse model after noise-induced hearing loss (NIHL). RNA sequencing of NIHL mouse cochleae revealed that CAE up-regulates genes involved in neurotransmitter synthesis, secretion, transport, and neuronal survival. Real-time qPCR validation showed that NIHL decreased the mRNA expression of genes related to neuronal function, such as Gabra1, Gad1, Slc32a1, CaMK2b, CaMKIV, and Slc17a7, while the CAE treatment significantly elevated these levels. In conclusion, our findings provide strong evidence that CAE protects against hearing loss by promoting sensory cell protection and enhancing the expression of genes critical for neuronal function and survival.

Korean Red Ginseng and ginsenosides have been studied for their efficacy against various diseases, including those related to aging. However, most aging studies use D-galactose to induce aging, which often does not accurately represent natural aging. This study aimed to verify improvements in auditory, cognitive, and liver function through administering red ginseng to an 18-month-old naturally aging mouse model. Auditory function was assessed using Auditory Brainstem Response (ABR) and Auditory Middle Latency Response (AMLR). Cognitive function was evaluated electrophysiologically with P300 and mismatch negativity (MMN), and behaviorally using the Y-maze. Additionally, biochemical tests and histological analysis were conducted to assess liver function. The effects of red ginseng on gene expression regulation were also examined in the cochlea, auditory cortex, and liver, focusing on age-related disease processes. Red ginseng significantly decreased hearing thresholds and improved central auditory function. It also enhanced cognitive behavior and function in response to external stimulation. Furthermore, red ginseng regulated alkaline phosphatase (ALP), albumin (Alb), and total protein (TP) levels, notably decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Hematoxylin and eosin (H&E) staining of liver tissue showed significant improvement in fat droplets. These effects appear to be mediated by the regulation of aging-related genes Dec, c-Jun, Stat5b, and Lims2. These results suggest that red ginseng improves auditory, cognitive, and liver functions in a naturally aged mouse model.