PCE-DP (D-pantothenyl alcohol) is an active ingredient in pharmaceuticals and cosmetics that prevents inflammation and promotes hair growth. In our previous randomized double-blind placebo-controlled UVB irradiation-induced pigmentation study using healthy Japanese men and women, we found that topical PCE-DP has brightening effects when used for 4 weeks. In this study, we examined four studies to clarify the molecular mechanism of PCE-DP activity: (i) epidermal turnover, (ii) melanosomal uptake of keratinocytes, (iii) melanocyte activation by keratinocytes, or (iv) melanin production in melanocytes. When PCE-DP was added to normal human epidermal keratinocytes (NHEK), the intracellular CoA and ATP concentrations significantly increased, and cell growth was significantly induced. Furthermore, epidermal turnover was enhanced by PCE-DP because the average projected area of corneocytes (APAc) significantly decreased after 4 weeks of daily topical application of PCE-DP to the skin of the medial upper arm. The mRNA expression level of adrenomedullin, a key factor for dendrite elongation in melanocytes, significantly decreased, and melanin uptake was inhibited by adding PCE-DP to the NHEK.　 The induction of endothelin-1 mRNA, which increases melanin synthesis in melanocytes, was significantly decreased by the addition of PCE-DP after UVB irradiation to the NHEK. On the other hand, when PCE-DP was added to melanocytes, no effects on cell growth or melanin synthesis were observed. This suggested that PCE-DP improves skin pigmentation by inducing epidermal turnover through the activation of ATP production in NHEK. This improvement mechanism may involve activation of the tricarboxylic acid cycle by increasing the intracellular CoA level. In addition, PCE-DP prevents skin pigmentation by inhibiting melanin uptake and inflammation after UVB irradiation in NHEK.

The molecular mechanism of PCE-DP, a novel brightening active ingredient.