This study by Kim et al. (2025) elucidates the protective effects of umbelliferone on epidermal barrier dysfunction induced by diabetic conditions. Chronic hyperglycemia disrupts tight junctions and compromises keratinocyte integrity, contributing to diabetic skin complications. Using hyperglycemia-exposed HaCaT keratinocytes and type 2 diabetic db/db mice, the authors demonstrate that umbelliferone markedly restores epidermal barrier homeostasis. Umbelliferone enhanced key structural and functional proteins, including filaggrin, ZO-1, and occludin, while improving epidermal hydration through upregulation of AQP3 and HAS2 and suppression of HYAL1. Importantly, it promoted keratinocyte migration under impaired wound-healing conditions by regulating F-actin organization, Rho GTPase signaling, and integrin β1 expression. Additionally, umbelliferone significantly reduced reactive oxygen species accumulation and prevented glucose-induced apoptosis. Collectively, these findings highlight umbelliferone as a promising therapeutic candidate for preserving skin barrier integrity and preventing diabetic skin complications through antioxidative, anti-apoptotic, and barrier-strengthening mechanisms.
