Protective Effects of Buckwheat and Isoquercitrin Against Noise‐Induced Hearing Loss in Mice: An Antioxidant Strategy Targeting the Nrf2/HO‐1 Pathway in Auditory Hair Cells

ABSTRACT Noise‐induced hearing loss (NIHL) is a significant clinical challenge primarily due to oxidative stress‐related mechanisms. This study investigates an antioxidant strategy using Buckwheat ( Fagopyrum esculentum Moench; BW) extracts and isoquercitrin (IQ), a major bioactive compound of BW, to prevent NIHL. Oral administration of BW before noise exposure significantly protected hearing, with histological analysis showing a reduction in hair cell (HC) loss in the cochlea. BW treatment also inhibited hydrogen peroxide (H 2 O 2 )‐induced cell death and activated the nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase 1 (HO‐1) pathway, reducing reactive oxygen species (ROS) levels. high‐performance liquid chromatography (HPLC) identified IQ as the primary bioactive compound, and in silico analysis suggested that IQ activates the Nrf2/HO‐1 pathway. In vitro and in vivo studies confirmed that IQ alleviated oxidative stress, reduced auditory brainstem response (ABR) threshold shifts, and protected against HC and ribbon synapse loss. While other compounds in BW may contribute synergistically, IQ is the key mediator of the protective effects, highlighting its potential as a promising alternative for preventing NIHL.