Quercetin 3- O -Galactoside Isolated from Limonium tetragonum Inhibits Melanogenesis by Regulating PKA/MITF Signaling and ERK Activation

• Published in: International journal of molecular sciences 2023-02, Vol.24 (4), p.3064
• Main Authors: Karadeniz, Fatih, Oh, Jung Hwan, Seo, Youngwan, Yang, Jiho, Lee, Hyunjung, Kong, Chang-Suk
• Format: Article
• Language: English
• Subjects: alpha-MSH - pharmacology; Animals; Cell Line, Tumor; Cyclic AMP response element-binding protein; Enzymes; Flavanols; Flavonoids; Galactosides; Hyperpigmentation; Hyperpigmentation - metabolism; In vivo methods and tests; Kinases; MAP kinase; Melanin; Melanins - metabolism; Melanocyte-stimulating hormone; Melanoma; Melanoma, Experimental - metabolism; Mice; Microphthalmia-associated transcription factor; Microphthalmia-Associated Transcription Factor - metabolism; Monophenol Monooxygenase - metabolism; Phosphorylation; Phytochemicals; Plumbaginaceae - metabolism; Protein kinase A; Proteins; Quercetin; Skin; Transcription factors; Tyrosinase; Ultraviolet radiation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043064

Quercetin 3- -galactoside (Q3G) is a common dietary flavanol that has been shown to possess several bioactivities, including anti-melanogenesis. However, how Q3G exerts its anti-melanogenic effect has not been studied. The current study, therefore aimed to investigate the anti-melanogenesis potential of Q3G and elucidate the underlying action mechanism in α-melanocyte-stimulating hormone ( -MSH)-induced hyperpigmentation model of B16F10 murine melanoma cells. Results showed that α-MSH stimulation significantly increased tyrosinase (TYR) and melanin production, which were significantly downregulated by Q3G treatment. The treatment with Q3G suppressed the transcriptional and protein expressions of melanogenesis-related enzymes TYR, tyrosinase related protein-1 (TRP-1), and TRP-2, along with the melanogenic transcription factor microphthalmia-associated transcription factor (MITF) in B16F10 cells. It was shown that Q3G downregulated MITF expression and suppressed its transcriptional activity by inhibiting the cAMP-dependent protein kinase A (PKA)-mediated activation of CREB and GSK3β. In addition, MAPK-regulated MITF activation signaling was also involved in the inhibition of melanin production by Q3G. The results suggest that the anti-melanogenic properties of Q3G rationalize further studies in vivo to confirm its action mechanism and consequent utilization as a cosmetic ingredient against hyperpigmentation.