Castanopsis echinocarpa extract attenuates diabetes-associated peripheral-to-central auditory electrophysiological dysfunction in streptozotocin-induced diabetic mice.

Abstract

Diabetes-associated auditory dysfunction may extend beyond cochlear threshold elevation and involve broader metabolic and auditory neural abnormalities. This study investigated whether Castanopsis echinocarpa extract (CAE) attenuates peripheral-to-central auditory electrophysiological dysfunction in streptozotocin (STZ)-induced diabetic mice and modulates related auditory and pancreatic stress responses. HEI-OC1 auditory cells were exposed to neomycin or inflammatory cytokines, and Tnf, Il1b, Trpv1, and Gjb2 mRNA expression was analyzed. Post-exposure otic hair cell recovery was assessed in neomycin-treated zebrafish larvae. MIN6 pancreatic β-cells and isolated pancreatic islet cells were used to evaluate oxidative and cytokine-induced β-cell injury. In vivo effects were examined in STZ-induced diabetic mice by measuring fasting blood glucose and auditory brainstem, middle-latency, and late-latency responses. CAE reduced neomycin- and cytokine-induced auditory cell injury, suppressed Tnf, Il1b, and Trpv1 upregulation, and partially restored Gjb2 expression in HEI-OC1 cells. CAE also supported otic hair cell recovery after neomycin injury. In pancreatic models, CAE attenuated H₂O₂- and cytokine-induced β-cell injury and reduced inflammatory gene responses. In STZ-induced diabetic mice, CAE lowered fasting blood glucose and improved ABR threshold shifts as well as AMLR and ALLR latency and amplitude abnormalities. These findings demonstrate concurrent improvements in metabolic and auditory outcomes following CAE treatment in STZ-induced diabetic mice and support further investigation of CAE as a multi-target candidate for diabetes-associated auditory dysfunction.