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Abstract
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 Trifolium pratense. 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.
Highlights
Melanin is produced by melanosomes in melanocytes, which are located in the epidermal-dermal junction and deliver melanosomes to surrounding keratinocytes
Since tyrosinase is a crucial enzyme in the regulation of melanogenesis, we examined the effect of pratol the up-regulation ofenzyme tyrosinase activity in B16F10 cells
It is reported that the 40 -O-methyl group on the B-ring of flavonoids plays a crucial role in the we evaluated the effect ofbypratol, a 7-hydroxy-4-methoxyflavone, onunderstood
Summary
Melanin is produced by melanosomes in melanocytes, which are located in the epidermal-dermal junction and deliver melanosomes to surrounding keratinocytes. Activators of tyrosinase are used as tanning agents or in the treatment of hair depigmentation They are used as functional materials in the preparation of products for treating other medical disorders such as vitiligo and albinism [3,4,5]. It is reported that activation of protein kinase A (PKA) can induce MITF expression via phosphorylation of cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB). This increases the transcription of tyrosinase, which results in the activation of melanin synthesis [12,13,14]. Recent studies have suggested that melanin synthesis is regulated by several signaling pathways, in particular, those involving ERK and phosphatidylinositol 3-kinase (PI3K)/AKT [15,16].
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