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

Abstract

Quercetin 3-O-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 (α-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.

6-Methylcoumarin Promotes Melanogenesis through the PKA/CREB, MAPK, AKT/PI3K, and GSK3β/β-Catenin Signaling Pathways

“…The transcriptional activity of microphthalmiaassociated transcription factor (MITF) induces melanogenesis by regulating the TYR, TRP-1, and TRP-2 expressions. External stimuli such as ultraviolet radiation, alpha-melanocytestimulating hormone (α-MSH), stem cell factors, and certain chemical agents can upregulate the expression of melanogenesis-controlling enzymes via stimulating the MITF expression and activity, which results in elevated melanin synthesis [5,6].…”

Comparative Study of Quercetin and Hyperoside: Antimicrobial Potential towards Food Spoilage Bacteria, Mode of Action and Molecular Docking

“…On the other hand, hyperoside was more effective in inhibiting bacterial growth. Both compounds have several OH groups; nonetheless, they are more prominent in the hyperoside structure due to the presence of the beta-D-galactosyl residue attached to its main skeleton [33]. At 1 MIC, hyperoside had a reduction rate of 1.138 log CFU/mL against SP and 0.381 log CFU/mL against PA after 24 h of incubation.…”