10(E)-Pentadecenoic Acid Inhibits Melanogenesis Partly Through Suppressing the Intracellular MITF/Tyrosinase Axis.

Melanogenesis, the biological process responsible for melanin synthesis, plays a crucial role in determining skin and hair color, photoprotection, and serving as a biomarker in various diseases. While various factors regulate melanogenesis, the role of fatty acids in this process remains underexplored. This study investigated the anti-melanogenic properties of 10(E)-pentadecenoic acid (10E-PDA) through both in silico and in vitro analyses. SwissSimilarity was utilized to predict the functional properties of 10E-PDA by comparing it with structurally similar lipids known to exhibit anti-melanogenic effects. Subsequent in vitro experiments demonstrated that 10E-PDA significantly reduced melanin production and intracellular tyrosinase activity in α-MSH (melanocyte-stimulating hormone)-stimulated B16F10 melanoma cells without exhibiting significant cytotoxicity at concentrations up to 15 μM. Further mechanistic studies revealed that 10E-PDA inhibited the nuclear translocation of microphthalmia-associated transcription factor (MITF), consistent with the decrease observed in p-MITF protein levels. It also decreased the mRNA levels of tyrosinase-related proteins (TRP-1, TRP-2) and tyrosinase, while reducing the protein levels of TRP-1 and tyrosinase, but not TRP-2. These findings suggest that 10E-PDA exerts its anti-melanogenic effects by modulating the MITF/tyrosinase axis, presenting potential therapeutic implications for skin pigmentation disorders.