Nicotinamide Mononucleotide Suppresses α-MSH-Induced Melanogenesis via Downregulation of Tyrosinase in B16F10 Cells

Abstract

Skin hyperpigmentation caused by excessive melanin production has led to increasing interest in the development of effective anti-melanogenic agents. In this study, the anti-melanogenic effects and underlying mechanisms of nicotinamide mononucleotide (NMN) were investigated using α-MSH-induced B16F10 melanoma cells. NMN maintained over 80% cell viability at concentrations below 0.5% and significantly reduced α-MSH-induced melanin accumulation and melanin content. In addition, in situ tyrosinase assay demonstrated that NMN effectively suppressed intracellular melanogenesis. However, NMN did not exhibit direct inhibitory activity against mushroom tyrosinase. Molecular docking analysis further revealed that NMN did not directly interact with the catalytic copper-binding site of tyrosinase. Furthermore, tyrosinase zymography and Western blot analyses demonstrated that NMN suppressed melanogenesis primarily through downregulation of tyrosinase protein expression rather than direct inhibition of tyrosinase catalytic activity. Collectively, these findings suggest that NMN suppresses melanogenesis through regulation of melanogenic signaling pathways, indicating its potential utility for hyperpigmentation-related applications.