Cosmetic applications of glucitol-core containing gallotannins from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract: inhibition of melanogenesis via down-regulation of tyrosinase and melanogenic gene expression in B16F10 melanoma cells

The red maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups attached to different positions of a 1,5-anhydro-d-glucitol core. While these glucitol-core containing gallotannins (GCGs) have reported anti-oxidant and anti-glycative effects, they have not yet been evaluated for their cosmetic applications. Herein, the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract [Maplifa((TM)); contains ca. 45% ginnalin A (GA) along with other GCGs] were investigated using enzyme and cellular assays. The GCGs showed anti-tyrosinase activity with IC50 values ranging from 101.4 to 1047.3 mu M and their mechanism of tyrosinase inhibition (using GA as a representative GCG) was evaluated by chelating and computational/modeling studies. GA reduced melanin content in murine melanoma B16F10 cells by 79.1 and 56.7% (at non-toxic concentrations of 25 and 50 mu M, respectively), and its mechanisms of anti-melanogenic effects were evaluated by using methods including fluorescent probe (DCF-DA), real-time PCR, and western blot experiments. These data indicated that GA was able to: (1) reduce the levels of reactive oxygen species, (2) down-regulate the expression of MITF, TYR, TRP-1, and TRP-2 gene levels in a time-dependent manner, and (3) significantly reduce protein expression of the TRP-2 gene. Therefore, the anti-melanogenic effects of red maple GCGs warrant further investigation of this proprietary natural product extract for potential cosmetic applications.