Abstract
The integrity of the skin barrier is crucial for reducing the risk and managing chronic skin conditions such as photoaging, eczema, and atopic dermatitis. Sesamol, a food-derived compound with strong antioxidant properties, is recognized for its anti-aging and skin-whitening effects. However, its role in skin barrier repair and protection remains insufficiently understood. This study aimed to explore the protective and restorative effects of sesamol on the skin barrier and to identify its potential molecular mechanisms. Our findings revealed that sesamol regulates the expression of aquaporin-3 (AQP3) and hyaluronan synthase 2 (HAS2) in HaCaT keratinocytes through the mitogen-activated protein kinase (MAPK) pathway. Additionally, Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cluster of differentiation 44 (CD44) were found to contribute to this regulation, leading to increased hyaluronic acid (HA) secretion. Molecular docking experiments further validated stable interactions between sesamol and key proteins, including MAPK, AQP3, and HAS2. In ultraviolet B (UVB)-induced photoaging HaCaT keratinocyte models, sesamol effectively suppressed hyaluronidase (HYAL) mRNA expression, thereby mitigating HA degradation. Similarly, in tumor necrosis factor-alpha (TNF-α)-induced dermatitis models, transepithelial electrical resistance (TEER) measurements demonstrated that sesamol repaired inflammatory skin barrier damage. Collectively, these findings suggest that sesamol has significant potential to combat photoaging and inflammatory skin disorders by strengthening and protecting the skin barrier. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-29463-8.