Ultrasound-assisted pumpkin tendril extracts inhibits melanogenesis by suppressing the CREB/MITF signaling pathway in B16F10 melanoma cells, zebrafish, and a human skin model

Agricultural byproducts are intermediate products generated during food processing and contain functional ingredients that are suitable for use in the green circular economy. This study aimed to demonstrate the skin-whitening effect of pumpkin tendril extract (PTE) using a mushroom tyrosinase assay, L-DOPA staining, qRT-PCR, western blotting, a zebrafish model, and a reconstituted 3D human skin model. PTE dose-dependently scavenged DPPH free radicals and inhibited melanogenesis stimulated by α-MSH without exhibiting cytotoxicity in 2D- and 3D-cultured B16F10 cells. Interestingly, PTE significantly reduced melanogenesis in zebrafish and 3D-pigmented human skin models. In addition, PTE notably downregulated the expression of proteins related to melanogenesis, such as MITF, TRP-1, TRP-2, and tyrosinase. Phosphorylation of CREB, an upregulator of MITF, was also attenuated by PTE treatment. Component analysis revealed that rutin is an active compound in PTE affecting melanogenesis. These results suggest that PTE suppresses melanogenesis and tyrosinase activity by regulating the CREB/MITF signaling pathway.