Pratol, an O-Methylated Flavone, Induces Melanogenesis in B16F10 Melanoma Cells via p-p38 and p-JNK Upregulation.
Tyrosinase is the rate-limiting enzyme critical for melanin synthesis. It controls pigmentation in the skin. Activation of tyrosinase is currently the most common approach in the development of tanning and haircare products. Pratol is a 7-hydroxy-4-methoxyflavone found in Trifoliumpratense. In this study, we investigated the effects of pratol on melanogenesis. We also studied the mechanism of action of pratol in B16F10 mouse melanoma cells. The cells were treated with various concentrations (6.25, 12.5, 25, and 50 μM) of pratol to observe its effects. The results showed that pratol significantly increased melanin content and tyrosinase activity in the cells without being cytotoxic. In addition, pratol strongly increased the expression of tyrosinase and tyrosinase-related protein-1 and 2 by enhancing the expression of microphthalmia-associated transcription factor. Furthermore, pratol stimulated melanogenesis via the phosphorylation of p38, c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinase (ERK). The findings from an assay searching for the inhibitor revealed that SB203580 (a specific p38 inhibitor) or SP600125 (a p-JNK inhibitor) attenuated pratol-induced cellular tyrosinase activity whereas PD98059 (an ERK inhibitor) did not. Additionally, pratol interfered with the phosphorylation of p-AKT. We also found that pratol-induced melanogenesis was reversed by H89, which is a specific protein kinase A inhibitor. The results suggest that, owing to its multi-functional properties, pratol may be a potential tanning agent or a therapeutic agent for hair depigmentation in the cosmetic industry.
['Chung|You Chul|YC|', 'Kim|Seoyeon|S|', 'Kim|Jin Hwa|JH|', 'Lee|Geun Soo|GS|', 'Lee|Jung No|JN|', 'Lee|Nam Ho|NH|', 'Hyun|Chang-Gu|CG|']
D000818:Animals D000873:Anthracenes D045744:Cell Line, Tumor D047309:Flavones D007093:Imidazoles D019746:Intramolecular Oxidoreductases D051379:Mice D015394:Molecular Structure D010088:Oxidoreductases D010766:Phosphorylation D016755:Proto-Oncogene Proteins c-jun D011725:Pyridines D029921:Trifolium
pratol flavone melanogenesis B16F10 melanoma cell p38 JNK AKT MAPK hypopigmentation