Anti-melanogenic Activity of Auraptene via ERK-mediated MITF Downregulation
Auraptene is the most abundant naturally occurring geranyloxycoumarin. It is primarilyisolated from plants belonging to the Rutaceae family, many of which, such as citrus fruits, areused as food in many countries. Auraptene is a biologically active secondary metabolite thatpossesses valuable properties. The aim of this study was to investigate the in vitro inhibitoryeffects of auraptene on melanogenesis and the enzymes associated with it, such as tyrosinase,tyrosinase-related protein (TRP)-1, and TRP-2, in B16F10 murine melanoma cells. We found thatauraptene significantly attenuated melanin synthesis and reduced the activity of intracellulartyrosinase, which was the rate-limiting melanogenic enzyme. Western blotting analysis showed thatauraptene decreased tyrosinase and TRP-2 protein expression. In addition, auraptene significantlydecreased the expression of microphthalmia-associated transcription factor (MITF), a key regulatorof melanogenesis. Extracellular signal-regulated kinase (ERK) activation has been reported to beinvolved in the inhibition of melanogenesis. Thus, we next investigated if the hypopigmentary effectsof auraptene were related to the activation of ERK. Auraptene was found to induce phosphorylationof ERK in a dose-dependent manner. Our results suggest that auraptene inhibits melanogenesisby activating the ERK pathway-mediated suppression of MITF and its downstream target genes,including tyrosinase. Therefore, auraptene may be used as a whitening agent in the development offunctional cosmetics.
