Citrus fruits are the major source of flavonoids for humans, and flavanones are the main flavonoids in the Citrus species. Among the Citrus flavanones, the glycoside derivatives of naringenin, naringin and narirutin, are the most abundant in grapefruit. The present study aimed to investigate the molecular events of melanogenesis induced by naringenin in murine B16-F10 melanoma cells. Melanin content, tyrosinase activity and Western blot analysis were performed to elucidate the possible underlying mechanisms. Exposure of melanoma cells to naringenin resulted in morphological changes accompanied by the induction of melanocyte differentiation-related markers, such as melanin synthesis, tyrosinase activity, and the expression of tyrosinase and microphthalmia-associated transcription factor (MITF). We also observed an increase in the intracellular accumulation of β-catenin as well as the phosphorylation of glycogen synthase kinase-3β (GSK3β) protein after treatment with naringenin. Moreover, the activity of phosphatidylinositol 3-kinase (PI3K) was up-regulated by naringenin since the phosphorylated level of downstream Akt protein was enhanced. Based on these results, we concluded that naringenin induced melanogenesis through the Wnt-β-catenin-signalling pathway.
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