Dietary flavonoid myricetin 3- O-galactoside suppresses α-melanocyte stimulating hormone-induced melanogenesis in B16F10 melanoma cells by regulating PKA and ERK1/2 activation

Z Naturforsch C J Biosci. 2023 Sep 14;78(11-12):399-407. doi: 10.1515/znc-2023-0039. Print 2023 Nov 27.

Abstract

Melanogenesis is the process where skin pigment melanin is produced through tyrosinase activity. Overproduction of melanin causes skin disorders such as freckles, spots, and hyperpigmentation. Myricetin 3-O-galactoside (M3G) is a dietary flavonoid with reported bioactivities. M3G was isolated from Limonium tetragonum and its anti-melanogenic properties were investigated in α-melanocyte stimulating hormone-stimulated B16F10 melanoma cells. The in vitro anti-melanogenic capacity of M3G was confirmed by inhibited tyrosinase and melanin production. M3G-mediated suppression of melanogenic proteins, tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related proteins (TRP)-1 and TRP-2, were confirmed by mRNA and protein levels, analyzed by RT-qPCR and Western blot, respectively. Furthermore, M3G suppressed Wnt signaling through the inhibition of PKA phosphorylation. M3G also suppressed the consequent phosphorylation of CREB and nuclear levels of MITF. Analysis of MAPK activation further revealed that M3G increased the activation of ERK1/2 while p38 and JNK activation remained unaffected. Results showed that M3G suppressed melanogenesis in B16F10 cells by decreasing tyrosinase production and therefore inhibiting melanin formation. A possible action mechanism was the suppression of CREB activation and upregulation of ERK phosphorylation which might cause the decreased nuclear levels of MITF. In conclusion, M3G was suggested to be a potential nutraceutical with anti-melanogenic properties.

Keywords: Limonium tetragonum; CREB; MITF; melanogenesis; myricetin 3-O-galactoside; tyrosinase.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Flavonoids / pharmacology
  • Galactosides
  • MAP Kinase Signaling System
  • Melanins / metabolism
  • Melanoma*
  • Melanoma, Experimental* / metabolism
  • Monophenol Monooxygenase
  • alpha-MSH / metabolism
  • alpha-MSH / pharmacology

Substances

  • Monophenol Monooxygenase
  • myricetin
  • Melanins
  • alpha-MSH
  • Flavonoids
  • Galactosides