Abstract
OBJECTIVE: To evaluate Oligopeptide-215, a biomimetic peptide engineered from amphibian skin secretions, for its dual capacity to restore skin barrier homeostasis by concurrently targeting physical barrier proteins and inflammatory pathways via JAK-STAT and NF-κB modulation. METHODS: In vitro models used UVB-damaged HaCaT keratinocytes, LPS-stimulated RAW264.7 macrophages, and IL-4/IL-13-stimulated HaCaT cells. Assays included cell viability (MTT), migration (scratch), adhesion, barrier proteins (FLG/LOR; ELISA/IF), signaling phosphoproteins (pJAK1/pTYK2/pSTAT3/pSTAT6/pNF-κB; IF), and inflammatory mediators (NO/PGE₂/TNF-α/IL-6/IL-1β; ELISA). RESULTS: Oligopeptide-215 antagonizes IL-13/IL-4-mediated JAK-STAT6/STAT3 signaling, thereby restoring expression of critical barrier proteins FLG and LOR. Additionally, it suppresses inflammatory responses by inhibiting NF-κB-dependent cytokine production. In UVB-damaged keratinocytes, Oligopeptide-215 promotes cellular repair through enhanced proliferation, adhesion, and migration. CONCLUSION: These findings revealed an innovative repairing mechanism combining physical barrier with immunologic barrier, and established Oligopeptide-215 as a potential skincare ingredient for skin barrier dysfunction.