Multifunctional Skin-Barrier Enhancement by Mentha piperita Extract: Keratinocyte Differentiation, Tight Junction Integrity, Anti-Stress and Anti-Inflammatory Effects in Macrophages

Purpose: This study evaluated the bioactivity of Mentha piperita extract (MPE) to determine its potential as a skin barrier-enhancing ingredient and assess its applicability as a functional cosmetic material. Methods: MPE was prepared by extracting M. piperita leaves with 70% ethanol. Barrier function was assessed by analyzing keratinocyte differentiation-related gene expression and cornified envelope formation in human keratinocytes. Tight junction (TJ) integrity was analyzed by evaluating the expression of genes related to TJ and their protein localization. Barrier homeostasis was assessed by measuring lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) production in immune cells and by determining 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibition as well as the recovery of cortisol-delayed wound healing in keratinocytes under stress conditions. Results: MPE increased the expression of keratinocyte differentiation–related genes, including involucrin (IVL), keratin 10 (KRT10), transglutaminase 1 (TGM1), filaggrin (FLG), caspase 14 (CASP14), and calpain 1 (CAPN1) and strongly promoted cornified envelope formation in a dose-dependent manner in HaCaT cells. The expression of TJ–related genes, such as claudin3 (CLDN3), claudin4 (CLDN4), claudin7 (CLDN7), occludin (OCLN), and zonula occludens-1 (ZO-1), was also elevated, with proteins CLDN4 and OCLN being upregulated at cell–cell junctions. In RAW 264.7 macrophages, MPE significantly reduced LPS-induced PGE2 production. Additionally, MPE suppressed 11β-HSD1 activity and improved wound closure delayed by cortisol treatment in HaCaT cells. Conclusion: These findings suggest that MPE is a potential multifunctional cosmetic ingredient that strengthens the skin barrier by promoting keratinocyte differentiation, enhancing TJ cohesion, reducing inflammation, and protecting against stress-induced damage.