Morus alba leaf extract modulates melanogenesis in enzymatic, cellular, and zebrafish models

Objective: To investigate the modulatory effects of a Morus alba leaf extract (FBCC-EP1619) on melanogenesis using enzymatic, cellular, and zebrafish models. Methods: Phytochemical profiling was conducted using UPLC-QTOF-MS/MS in negative ion mode. Mushroom tyrosinase inhibition was assessed in vitro. Cytotoxicity and melanin content were measured in B16F10 melanoma cells under basal and α-melanocyte-stimulating hormone (α-MSH-stimulated conditions. An in vivo pigmentation model was established using α-MSH-treated zebrafish larvae, and pigmentation was quantified. Expression of melanogenesis-related genes ( mitfa and tyr ) was analyzed by RT-qPCR. Results: FBCC-EP1619 contained diverse phenolic and lipid-derived metabolites. The extract significantly inhibited mushroom tyrosinase activity in a concentration-dependent manner. In B16F10 cells, it did not induce cytotoxicity but increased melanin production. In contrast, in α-MSH-stimulated zebrafish larvae, FBCC-EP1619 attenuated hyperpigmentation and significantly downregulated mitfa and tyr expression, indicating system- and stimulus-dependent regulation. Conclusions: FBCC-EP1619 differentially modulates melanogenesis depending on the biological system, enhancing basal melanin production in vitro while suppressing α-MSH-induced pigmentation in vivo. These findings provide pharmacological support for the ethnopharmacological relevance of Morus alba leaves and warrant further investigation into the underlying molecular mechanisms.