Sulforaphane Ameliorates High-Glucose-Induced Damage in a Diabetic Foot Ulcer Cell Model by Activating the Nrf2 Pathway to Improve Mitochondrial Function and Suppress Inflammation

Background/Objectives: Diabetic foot ulcers (DFUs) are a common and challenging complication of diabetes, significantly impacting the quality of life for patients due to impaired wound healing. Exploring effective and targeted therapies for DFUs is therefore both important and meaningful. Sulforaphane (SFN), a natural bioactive compound found in cruciferous vegetables, shows promise in this area. However, its role and underlying mechanisms in promoting wound healing in DFUs have not been fully understood. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured under high-glucose conditions to establish an in vitro diabetic model. Cell viability, inflammation, apoptosis, and mitochondrial function were assessed. The expression and activation of Nrf2 were examined following SFN treatment. Additionally, Nrf2 overexpression was performed to validate its role in mediating the protective effects of SFN under high-glucose stress. Results: High-glucose conditions significantly reduced HUVEC viability and increased inflammation, apoptosis, and mitochondrial dysfunction. Treatment with SFN effectively counteracted these detrimental effects. SFN robustly activated Nrf2 signaling, and overexpression of Nrf2 recapitulated the protective effects of SFN, attenuating cellular damage under high-glucose conditions. Conclusions: SFN activates Nrf2 expression and protects HUVECs from high-glucose-induced injury by improving cell viability, mitochondrial function, and inflammatory response. These findings suggest that SFN may serve as a promising targeted therapy for diabetic foot ulcers.