Johann W. Wiechers, A. V. Rawlings, C. Garcia
Apr 1, 2005
Citations
1
Influential Citations
39
Citations
Journal
International Journal of Cosmetic Science
Abstract
Octadecenedioic acid is known as a skin whitening agent but its activity is not mediated via a direct inhibition of tyrosinase. Based on the secondary properties of this molecule, such as its anti‐inflammatory and anti‐ageing effects, we postulated that octadecenedioic acid interacted with the peroxisome proliferator‐activated receptor (PPAR) as this nuclear receptor also mediates these effects. Using reporter gene technology, we were indeed able to demonstrate binding of octadecenedioic acid to all three PPAR subtypes, in particular PPARγ with an EC50‐value of approx. 1 × 10−6 m. Binding to PPARγ of octadecenedioic acid or rosiglitazone, a known pharmaceutical PPARγ agonist, led to reduced melanogenesis. Subsequently also tyrosinase mRNA (as measured by real‐time polymerase chain reaction) and tyrosinase levels (as measured by Western blot) were reduced, suggesting the existence of a complete novel mechanism of skin whitening agents: binding to PPARγ results in reduced tyrosinase mRNA expression which in turn results in less tyrosinase being formed. This in turn leads to reduced melanogenesis both in vitro and in vivo Because octadecenedioic acid binds not only to PPARγ but also to PPARα and PPARδ, other efficacies mediated via these receptors may also be expected.