Study on improvement of skin barrier by PPAR-α agonists derived from natural materials

Peroxisome proliferator-activated receptors (PPAR)-α plays an important role in epidermal differentiation and barrier recovery, and topical treatment with PPAR-α agonists restores epidermal homeostasis in essential fatty acid deficiency and permeability barrier in skin disruptions. We showed that the treatment with Eruca sativa extract (ES) resulted in a significant increase in the transactivation activity of peroxisome proliferator activated receptor response element such as PPAR-α and suppression in the expression of inflammatory cytokine and antimicrobial peptides. In addition, ES extract promotes the expression of filaggrin related to skin barrier protection. Scutellaria baicalensis extract (SBE) promotes the expression of protein related to cornified envelope (CE) formation such as involucrin. We performed structure-based pharmacophore screening to search for a novel PPAR-α agonist. Caffeic acid was ultimately selected and evaluated for its effects on keratinocyte differentiation and epidermal permeability barrier. Caffeic acid increases the transactivation activity of PPRE and CE formation in keratinocytes. In addition, caffeic acid promotes the expression of genes and proteins related to CE formation such as involucrin and transglutaminase-1. These results indicate that PPAR-α agonists may be an appropriate material for improving skin barrier function as a skin therapeutic agent for atopic dermatitis.