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.