Caffeic acid induces keratinocyte differentiation by activation of PPAR-α.

ObjectivesPeroxisome proliferator-activated receptors (PPAR)- plays an important role in epidermal differentiation and barrier recovery, and topical treatment with PPAR- agonists restores epidermal homeostasis in essential fatty acid deficiency and permeability barrier in skin disruptions. Therefore, we performed structure-based pharmacophore screening to search for a novel PPAR- agonist. Caffeic acid was ultimately selected and evaluated for its effects on keratinocyte differentiation and epidermal permeability barrier. MethodsThe transactivation activity of PPAR-responsive element (PPRE) and cornified envelope (CE) formation were assayed. Also, immunoblot analysis and anti-oxidant activity were investigated on caffeic acid. Key findingsCaffeic 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. Additionally, anti-oxidant activity were improved by caffeic acid. ConclusionsCaffeic acid can promote keratinocyte differentiation and restore skin barrier homeostasis and is suggested to be an appropriate skin therapeutic agent for improving epidermal permeability barrier function.