Isoquercitrin induces melanogenesis in B16F10 melanoma cells and zebrafish via the p38 and PKA/CREB signaling pathways: an experimental study.

BACKGROUND

Isoquercitrin (IQ), a flavonoid with anticancer, antioxidant, anti-inflammatory, and antiallergic properties, exhibits dual effects on B16F10 melanoma cells by suppressing cell viability and inducing hyperpigmentation. This study investigated the molecular mechanisms underlying IQ-induced melanogenesis in vitro and in vivo, highlighting the potential of IQ in the treatment of vitiligo.

METHODS

B16F10 melanoma cells and zebrafish were treated with various IQ concentrations and melanogenesis was evaluated using western blotting, a tyrosinase activity assay, and microscopic observation. In addition, signaling pathway modulators and IQ were used to confirm the signaling pathways involved in IQ-induced melanogenesis.

RESULTS

IQ treatment of B16F10 melanoma cells enhanced tyrosinase activity and upregulated melanogenesis-associated proteins, including microphthalmia-associated transcription factor and tyrosinase, via the p38 and protein kinase A (PKA)/cyclic AMP response element-binding protein (CREB) signaling pathways. Cotreatment with pathway-specific inhibitors (SB203580 for p38 and H89 for PKA/CREB) attenuated melanogenesis, whereas forskolin (a PKA/CREB activator) enhanced melanogenesis, confirming the involvement of these signaling pathways. In zebrafish, IQ treatment significantly increased melanophore production in the dorsal region following hypopigmentation induction with 1-phenyl-2-thiourea (PTU). Similar to that in B16F10 melanoma cells, SB203580 and H89 suppressed IQ-induced pigmentation, whereas forskolin enhanced it.

CONCLUSION

These findings demonstrate that IQ promotes melanogenesis in vitro and in vivo through activation of the p38 and PKA/CREB signaling pathways, supporting its potential as a therapeutic agent for vitiligo.