Antimelanogenic Effects of Lactobacillus helveticus–Fermented Whey in a-MSH-Stimulated Melanoma Cells and UV-Irradiated Mice

Introduction: Lactic acid bacteria have various beneficial effects on humans and are widely used in the production of fermented foods. The whey generated by lactic acid bacteria during milk fermentation has been reported to increase the expression of skin moisturizing factors. This study aimed to elucidate the effects of whey on ultraviolet (UV)-induced skin pigmentation. Methods: The effects of α-melanocyte-stimulating hormone (α-MSH) alone or in combination with whey on melanin production were evaluated in mouse melanoma B16 cells. In addition, whey was topically applied to UV-irradiated HRM-2 mice, and the skin melanin content and the expression levels of melanogenesis-related enzymes (tyrosinase [TYR], tyrosinase-related protein 1 [TYRP1], and dopachrome tautomerase [DCT]) and microphthalmia-associated transcription factor (Mitf) were analyzed. Results: Whey significantly suppressed the α-MSH-induced melanin production increase in B16 cells in a concentration-dependent manner. UV irradiation significantly increased the skin melanin content in HRM-2 mice compared to that in the control group, which was markedly reduced by whey treatment. Furthermore, whey significantly inhibited the UV-induced upregulation of melanogenesis-related enzymes. Similarly, whey suppressed the expression of Mitf, a key transcription factor that regulates melanogenic enzyme expression. Conclusion: Topical application of whey suppressed UV-induced skin pigmentation by inhibiting Mitf expression, leading to reduced expression of downstream melanogenic enzymes, TYR, TYRP1, and DCT. These findings suggest that whey is a promising cosmetic ingredient for preventing or attenuating the progression of skin pigmentation.