Anti-melanogenic Activity of Gagunin D by Modulation of Tyrosinase Expression and Degradation

Abstract

Tyrosinase is the rate-limiting enzyme critical for melanin biosynthesis and controls pigmentation in the skin. Inhibition of tyrosinase has so far been the most common approach in the development of skin-whitening cosmetics. A number of tyrosinase inhibitors are used as cosmetic formulations. However, in this present study, a balance between tyrosinase expression and degradation is considered as a new target for skin whitening agent. Gagunin D (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas sp., has exhibited cytotoxicity toward human leukemia cells (K562). However, the effect of GD on normal cells and the molecular mechanisms of action remain to be elucidated. In this study, The anti-melanogenic activity of GD and its precise underlying mechanisms in mouse originated melan-a cells were identified. GD significantly inhibited melanin synthesis in the melan-a cells without cytotoxicity and had an effect on a reconstructed human skin model composed of human epidermis and melanocytes. Further analysis revealed that GD suppressed the expression of tyrosinase and increased the rate of tyrosinase degradation. GD also inhibited tyrosinase enzymatic activity. In addition, GD effectively suppressed the expression of proteins associated with melanosome-transfer. These findings suggest that GD is a potential candidate for cosmetic formulations due to its multi-functional properties which replaces tyrosinase inhibitor.