Docosatrienoic Acid Inhibits Melanogenesis Partly through Suppressing the Intracellular MITF/Tyrosinase Axis.

Melanogenesis, essential for skin photoprotection and pigmentation, can lead to disorders like melasma and hyperpigmentation, which are challenging to treat and affect quality of life. Docosatrienoic acid (DTA), a polyunsaturated omega-3 fatty acid, has been identified as a potential regulator of skin aging. This study investigates DTA's effects on melanogenesis and its underlying molecular mechanisms using in silico and in vitro analyses. SwissSimilarity analysis revealed that DTA shares close structural similarities with known anti-melanogenic lipids, suggesting it may inhibit melanogenesis in similar manners. Our results demonstrated that DTA reduces melanin content and intracellular tyrosinase activity in B16F10 cells, significantly downregulating the mRNA expression of , , and by inhibiting MITF translocation to the nucleus. While DTA exhibited mild inhibitory effects on mushroom tyrosinase activity and antioxidant properties at higher concentrations, direct inhibition of tyrosinase is likely not the primary mechanism, as the observed anti-melanogenic effects occurred at much lower concentrations compared to those required for direct tyrosinase inhibition. Together, DTA-mediated modulation of MITF and tyrosinase mRNA expression offers a novel approach to treating hyperpigmentation. DTA's potential extends into the cosmetic industry, enhancing product stability, functionality, and aesthetics. Further research is needed to explore DTA's broader applications in skincare and cosmetic formulations.