An Adhesive Peptide Derived from Mussel Protein Alleviates LL37-Induced Rosacea Through Anti-Inflammatory and Anti-Angiogenic Mechanisms

Rosacea is a chronic inflammatory skin condition characterized by persistent erythema and telangiectasia, often accompanied by skin barrier disruption and abnormal angiogenesis. Currently, peptide-based therapies for rosacea are limited, and existing drugs still present certain limitations and side effects. Peptides have the advantage of being relatively safe and exhibiting high target specificity, which can reduce the risk of adverse effects. Considering these points, this study aimed to explore the adhesive peptide AdhPep3 (AYDPGYK) as a potential therapeutic candidate for rosacea. AdhPep3 was designed based on protein sequences with cell junction properties and has the potential to enhance skin barrier-related protein expression by improving cell–cell adhesion and increasing adhesion-related protein levels. In LL-37-stimulated HaCaT cells, AdhPep3 effectively alleviated skin inflammation and inhibited the Toll-like receptor–nuclear factor kappa B (TLR2–NFκB) signaling pathway. Additionally, in LL-37-stimulated human umbilical vein endothelial cells (HUVECs), it reduced cell migration and the expression of angiogenesis-related proteins. Since AdhPep3 demonstrated anti-inflammatory and anti-angiogenic effects at the in vitro level, it may serve as a potential therapeutic agent for rosacea. Moreover, by increasing the expression of skin barrier and tight junction-related proteins, AdhPep3 shows potential for development as a cosmetic ingredient to improve skin health.