Abstract
Skin barrier dysfunction and thin epidermis are hallmarks of sensitive skin and contribute to premature aging. Avenanthramides are the primary bioactive components of colloidal oatmeal, a commonly used treatment to enhance skin barrier function. This study investigated the relationship between skin barrier function and epidermal characteristics and explored the potential of dihydroavenanthramide D (dhAvD), a synthetic avenanthramide, to improve the skin barrier. We observed a significant correlation between impaired skin barrier function and decreased epidermal thickness, suggesting that a weakened barrier contributes to increased sensitivity. Our in vitro results in HaCaT cells demonstrated that dhAvD enhances keratinocyte proliferation, migration, and tight junction protein expression, thereby strengthening the skin barrier. To mimic skin barrier dysfunction, we treated keratinocytes and full-thickness skin equivalents with IL-4 and IL-13, cytokines that are implicated in atopic dermatitis, and confirmed the downregulation of tight junction and differentiation markers. Furthermore, dhAvD treatment restored the barrier function and normalized the expression of key epidermal components, such as tight junction proteins and natural moisturizing factors, in keratinocytes treated with inflammatory cytokines. In the reconstructed human skin model, dhAvD promoted both epidermal and dermal restoration. These findings suggest that dhAvD has the potential to alleviate skin sensitivity and improve skin barrier function.