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 tyrosinase, TRP-1, and TRP-2 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.

Sargassum serratifolium (S. serratifolium), listed in the Food Code, is known for its antioxidant and anti-inflammatory properties and is used in cosmetic applications. However, due to limited industrial utilization and overaccumulation in marine environments, Sargassum has been designated as a marine pollutant by the UN Environment Agency. To improve resource efficiency and reduce environmental burden, this study developed a dual-extraction strategy to isolate extracellular vesicles (EVs) and extract ethanol-soluble substances from the same S. serratifolium biomass. The extracellular vesicles derived from S. serratifolium (SEVs) were isolated and characterized based on their particle size, morphology, concentration, and cargo molecules, including mRNA and proteins. Their antioxidant and anti-inflammatory activities were evaluated using cellular assays, while their effects on melanogenesis and melanosome transport were assessed in B16F10 melanoma cells. Transcriptomic analysis by RNA sequencing was further performed to investigate the molecular pathways involved in SEV-mediated regulation of melanosome transport. SEVs isolation did not affect the yield or biological activity of the S. serratifolium ethanol-soluble fraction. Based on our previous finding that the ethanol extract of S. serratifolium (ESS) suppresses melanin synthesis, the present study focused on investigating the effects and mechanisms of SEVs on melanogenesis and melanosome transport. SEVs were nanoscale vesicles containing mRNA and proteins and showed antioxidant and anti-inflammatory effects in cellular assays. Although SEVs did not reduce melanin production in B16F10 cells, they significantly inhibited melanosome transport. RNA sequencing suggested that SEVs regulated melanosome transport through pathways related to the extracellular matrix, actin filament organization, and calcium ion homeostasis. These findings suggest that SEVs exert anti-melanogenic effects by targeting melanosome transport, providing a complementary mechanism to the previously reported inhibition of melanin synthesis by ESS. These findings demonstrate a sustainable strategy for producing functional EVs and bioactive extracts from a single S. serratifolium biomass source and support their potential use in cosmetic or therapeutic applications targeting hyperpigmentation.