Abstract
The aim of this study was to investigate the anti-melanogenic effects and underlying mechanisms of PFRMY (Pro-Phe-Arg-Met-Tyr), a pentapeptide derived from tilapia skin (Oreochromis niloticus), using B16F10 murine melanoma cells. Treatment with PFRMY (1.0 mg/mL) significantly reduced intracellular melanin content and tyrosinase (TYR) activity by 39.55 ± 1.51% and 32.46 ± 1.31%, respectively. RT-PCR and Western blotting analyses revealed that PFRMY suppressed melanogenesis through the α-MSH/PKA/CREB signaling pathway. Notably, PFRMY reversed α-MSH-induced upregulation of key downstream factors including PKA, CREB, MITF, and TYR, while showing minimal effects on the protein expression of MC1R or α-MSH. Molecular docking further suggested that PFRMY binds to MC1R with higher affinity than α-MSH, potentially occupying the ligand-binding site and thereby interfering with downstream signaling. Collectively, these findings demonstrate that PFRMY effectively inhibits melanogenesis by competitively antagonizing the α-MSH/MC1R axis, highlighting its potential as a safe and efficacious ingredient for hyperpigmentation treatment and cosmetic applications.