Anti-Melanogenic Effects of Hydroxyectoine via MITF Inhibition by JNK, p38, and AKT Pathways in B16F10 Melanoma Cells

Melanin plays a role in determining human skin color of a person, and a large amount of melanin makes the skin color look darkened. The proper amount of melanin formation protects our skin from UV radiation, but excessive melanin production causes hyperpigmentation and leads to freckles, melasma, and lentigo. In this study, we investigated the inhibitory effect of hydroxyectoine on melanogenesis and its mechanism in B16F10 cells. Melanin content and cellular tyrosinase activity were determined. The expression of microphthalmia-associated transcription factor (MITF), and the activities of tyrosinase and other melanogenesis-related enzymes, such as tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2, were also examined. Hydroxyectoine treatment significantly inhibited melanin production and intracellular tyrosinase activity in a dose-dependent manner. Western blot analysis showed that hydroxyectoine also reduced the expressions of tyrosinase and TRP-1. In addition, hydroxyectoine significantly reduced the expression of MITF, a major regulator of melanin production, and inhibited the phosphorylation of p38, c-Jun N-terminal kinase, and activated the protein kinase B. The results demonstrated that hydroxyectoine inhibits the expression of MITF through the inhibition or activation of melanin-related signaling pathways and downregulates melanogenesis by inhibiting melanogenic enzyme expression and tyrosinase activity. Hydroxyectoine has potential value in functional cosmetics applications, such as whitening.