Topical application of pseudo-ceramide alleviated inflammatory symptoms and reduced topical glucocorticoid-induced adverse effects through peroxisome proliferator activated receptor alpha activation

Abstract

Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors with various biological effects. Through a lot of studies, it has been proved that topical PPAR activators can improve the epidermal permeability barrier function, as well as relieve the inflammatory responses in acute and chronic irritation models. Those results also suggest that topical PPAR activator application can be a potential therapeutic regimen for the various inflammatory skin diseases, including atopic dermatitis (AD).Pseudo-ceramides are originally developed as structural substitutes for the ceramides, which are the major components for the stratum corneum intercellular lipids, and are one of the mostly used ingredients for moisturizers. However, the biological activities of pseudo-ceramides have not been studied extensively. In this study, the biological activity of PC-9S, one the pseudo-ceramides commercially available, has been investigated, focusing on the anti-inflammatory and barrier improving effects. As a result, anti-inflammatory activity of PC-9S was observed in both TPA-induced acute irritation model and oxazolone-induced chronic skin irritation model. Improvements of skin barrier functions, evaluated by trans-epidermal water loss (TEWL), skin hydration, and skin surface pH were also observed. Topical PC-9S application also resulted in increased expressions of differentiation marker proteins, involucrin and loricrin, in epidermis. It was also observed that topical PC-9S up-regulated the expression of anti-microbial peptides (AMPs) in epidermis, while suppressed TLR-2 expression, in oxazolone-induced chronic skin irritation model. Interestingly, topical application of PC-9S with glucocorticoids (GCs) prevented the adverse effects of GCs and also down-regulated the 11β-hydroxysteroid dehydrogenase type 1 (HSD11β1) expression in epidermis. In conclusion, this study demonstrates that PC-9S, a pseudo-ceramide used for opical moisturizers, has anti-inflammatory activities and skin barrier function improving effects, and co-application with topical glucocorticoid can reduce the GC-induced adverse effects. These results provide further evidences for the currently accepted therapeutic benefits of pseudo-ceramides.