Effect of 3,6-anhydro-l-galactose on α-melanocyte Stimulating Hormone-induced Melanogenesis in Human Melanocytes and a Skin-equivalent Model

3,6-Anhydro-l-galactose (l-AHG) is a bioactive sugar that is a major component of agarose. Recently, l-AHG was reported to have anti-melanogenic potential in human epidermal melanocytes (HEMs) and B16F10 melanoma cells; however, its underlying molecular mechanisms remain unknown. At noncytotoxic concentrations, l-AHG has been shown to inhibit alpha-melanocyte-stimulating hormone-induced melanin synthesis in various cell models, including HEMs, melan-a cells, and B16F10 cells. Although l-AHG did not inhibit tyrosinase activity in vitro, reverse transcription-polymerase chain reaction results demonstrated that the anti-melanogenic effect of l-AHG was mediated by transcriptional repression of melanogenesis-related genes, including tyrosinase, tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and microphthalmia-associated transcription factor (MITF) in HEMs. Western blot analysis showed that l-AHG effectively attenuated α-melanocyte-stimulating hormone-induced melanogenic proteins by inhibiting cyclic adenosine monophosphate/cyclic adenosine monophosphate-dependent protein kinase, mitogen-activated protein kinase, and Akt signaling pathways in HEMs. Topical application of l-AHG significantly ameliorated melanin production in a 3D pigmented human skin model. Collectively, these results suggest that l-AHG could be utilized as novel cosmetic compounds with skin-whitening efficacy.