Abstract
With growing concerns over the safety of synthetic substances, the development of plant-derived alternatives with minimal adverse effects has gained significant attention. Carica papaya L. peel contains a rich profile of bioactive compounds, including papain, flavonoids, and vitamin C, which exhibit potent antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of an ethanol extract of C. papaya peel (EECP) on inflammation and skin barrier dysfunction in a mouse model of contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Mice were treated by applying EECP at three different levels (60, 80, and 600 μg) to dorsal skin for six days. Skin lesion severity, skin color, skin barrier function (SBF, as indicated by water content and water-holding capacity (WHC)), histopathological abnormalities, cytokine levels, filaggrin and Intercellular Adhesion Molecule-1 (ICAM-1) expression, and phosphorylation of MAPK (Mitogen-Activated Protein Kinase) signaling molecules were assessed. EECP treatment significantly alleviated the CD-associated dermal symptoms induced by DNFB, including skin fissures, scabbing, roughness, changes in color, water content, and WHC, as well as petechiae. EECP also prevented histopathological abnormalities such as epidermal hyperplasia, spongiotic changes, and immune cell infiltration. In addition, EECP suppressed the production of pro-inflammatory cytokines, viz. TNF-α, IFN-γ, IL-6, and MCP-1. In addition, EECP restored filaggrin expression and inhibited ERK (Extracellular signal-regulated kinases) phosphorylation and ICAM-1 expression in HaCaT cells. In summary, C. papaya peel demonstrated therapeutic potential by effectively suppressing inflammation and restoring SBF. These findings support the potential use of EECP as a safe and effective botanical candidate for the treatment of CD and the promotion of overall skin health