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

Abstract

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.

Keywords

Morus alba / Melanogenesis / Tyrosinase / Hyperpigmentation / α-MSH / Zebrafish model

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This research was supported by the 2025 scientific promotion program funded by Jeju National University.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

MHDK conducted conceptualization, data curation, formal analysis, investigation, methodology, validation, and visualization, and wrote original draft of manuscript. SYL was responsible for data curation, formal analysis, investigation, methodology, validation, and visualization. YHC contributed to conceptualization, validation, and visualization, and reviewed and edited the manuscript. SMJ and CSL were responsible for resources, investigation, and methodology. HWR contributed to data curation, formal analysis, investigation, methodology, validation, and visualization, and wrote original draft of manuscript. GYK conceptualized and supervised the study and contributed to manuscript review and editing. All authors approved the final manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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