Potential of ononin as a safe and effective anti-melanogenic agent: In vitro and zebrafish embryo study

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Eur J Pharmacol. 2025 Aug 7;1005:178052. doi: 10.1016/j.ejphar.2025.178052. Online ahead of print.

ABSTRACT

Melanin production influences skin and hair coloration, and excessive melanin synthesis can lead to hyperpigmentation disorders. Melanogenesis is regulated by proteins such as Tyr, MITF, TRP1, TRP2, CREB, PI3K, and MC1R. While ononin has shown potential anti-melanogenic properties, its effects and underlying mechanisms remain unclear. The purpose of this study was to investigate the anti-melanogenic effects of ononin and evaluate its safety on zebrafish embryos. In vitro experiments with B16F10 cells were conducted to assess melanogenesis-related protein expression, and zebrafish embryos were treated with various concentrations of ononin to observe pigmentation changes. Western blotting was used to measure protein levels, and histopathological analysis was performed to evaluate safety in zebrafish. Results showed that ononin treatment led to a dose-dependent decrease in Tyr, MITF, TRP1, TRP2, CREB, PI3K, and MC1R expression in B16F10 cells. In zebrafish embryos, 10 μM ononin significantly suppressed pigmentation compared to the control group. Histopathological analysis revealed no liver damage, including no cytoplasmic vacuolization, hepatic necrosis, or lymphocyte infiltration in ononin-treated groups. In conclusion, ononin effectively suppresses melanin production in B16F10 cells and zebrafish embryos without adverse liver effects. These findings suggest that ononin holds promise as a therapeutic agent for hyperpigmentation disorders and warrants further research into its mechanisms and clinical applications.

PMID:40783161 | DOI:10.1016/j.ejphar.2025.178052