Oral ceramide attenuates ultraviolet Binduced epidermal dysregulation and hyperpigmentation by modulating MITF...

Ultraviolet B (UVB) irradiation induces epidermal dysregulation characterized by hyperpigmentation, barrier dysfunction, and abnormal keratinocyte differentiation, contributing to photoaging and skin disorders. Ceramides are key structural lipids of the stratum corneum and are widely used as topical agents to support barrier integrity. However, the role of oral ceramide in UVB-induced skin damage remains unclear. In this study, we investigated whether oral ceramide administration attenuates UVB-induced skin alterations in HRM-2 hairless mice. Mice were repeatedly exposed to UVB and orally administered ceramide (2.5 or 7.5 mg/kg/day). UVB exposure increased dorsal skin pigmentation, epidermal thickness, microphthalmia-associated transcription factor (MITF) expression, and melanogenesis-related gene transcription, while tending to reduce skin hydration. Oral ceramide markedly suppressed these changes and enhanced skin moisture content without affecting general health status. Immunofluorescence and reverse transcription-quantitative PCR analyses revealed a reduction in the number of MITF-positive cells and downregulation of Tyrp1, Mc1r, and Mitf. RNA sequencing analysis further demonstrated that ceramide counteracted UVB-induced transcriptional dysregulation by suppressing keratinization pathways and promoting retinoic acid receptor- and wound-healing-associated signaling. These findings indicate that oral ceramide not only reduces melanin synthesis but also promotes the recovery of epidermal homeostasis by modulating melanocyte activity, keratinocyte differentiation, and barrier function. Accordingly, oral ceramide attenuates UVB-induced skin pigmentation by suppressing MITF-dependent melanogenesis and restoring skin homeostasis, highlighting its potential as a therapeutic agent for photodamage-associated skin disorders.