Abstract
Sugars are ubiquitous in organisms and well-known cosmetic ingredients for moisturizing skin with minimal side-effects. Glucose, a simple sugar used as an energy source by living cells, is often used in skin care products. Several reports have demonstrated that sugar and sugar-related compounds have anti-melanogenic effects on melanocytes. However, the underlying molecular mechanism by which glucose inhibits melanin synthesis is unknown, even though glucose is used as a whitening as well as moisturizing ingredient in cosmetics. Herein, we found that glucose significantly reduced the melanin content of α-melanocyte-stimulating hormone (MSH)-stimulated B16 cells and darkly pigmented normal human melanocytes with no signs of cytotoxicity. Furthermore, topical treatment of glucose clearly demonstrated its whitening efficacy through photography, Fontana-Masson (F&M) staining, and multi-photon microscopy in a pigmented 3D human skin model, MelanoDerm. However, glucose did not alter the gene expression or protein levels of major melanogenic proteins in melanocytes. While glucose potently decreased intracellular tyrosinase activity in melanocytes, it did not reduce mushroom tyrosinase activity in a cell-free experimental system. However, glucose was metabolized into lactic acid, which can powerfully suppress tyrosinase activity. Thus, we concluded that glucose indirectly inhibits tyrosinase activity through conversion into lactic acid, explaining its anti-melanogenic effects in melanocytes.
Highlights
Melanogenesis is the process of melanin production and is essential for skin protection
Based on the cytotoxicity data, B16 cells were treated with various concentrations of glucose for 72 h in the presence of α-melanocyte-stimulating hormone (MSH), an inducer of melanogenesis
When melanin content was determined after glucose treatment of normal human melanocytes (NHMs) for 4 days, we found that melanin content decreased in a dose-dependent manner (Figure 1F)
Summary
Melanogenesis is the process of melanin production and is essential for skin protection. The role of sugars in melanogenesis has been highlighted by studies investigating the effect of glycosylation on the pigmentation phenotype of melanocytes and the roles of sugar residues on the catalytic activity of tyrosinase [5,6,7]. Recent studies have showed that sugar-related compounds inhibit tyrosinase expression or activation as well as alter its glycosylation. Galacturonic acid exerts a whitening effect through regulation of tyrosinase activity and expression in B16 murine melanoma cells and a human skin equivalent [9]. Similar to tyrosinase maturation by proper glycosylation, the expression or activity of CNN could be a target of anti-melanogenic agents [11]. We investigated the anti-melanogenic effects of glucose on B16 murine melanoma cells and normal human melanocytes. We propose that the whitening effect of glucose is dependent on lactic acid production, resulting in tyrosinase inactivation
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