Abstract
Melanin pigment produced in melanocytes plays a protective role against ultraviolet radiation. Selective destruction of melanocytes causes chronic depigmentation conditions such as vitiligo, for which there are very few specific medical treatments. Here, we found that fraxinol, a natural coumarin from Fraxinus plants, effectively stimulated melanogenesis. Treatment of B16-F10 cells with fraxinol increased the melanin content and tyrosinase activity in a concentration-dependent manner without causing cytotoxicity. Additionally, fraxinol enhanced the mRNA expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. Fraxinol also increased the expression of microphthalmia-associated transcription factor at both mRNA and protein levels. Fraxinol upregulated the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). Furthermore, H89, a cAMP–dependent protein kinase A inhibitor, decreased fraxinol-induced CREB phosphorylation and microphthalmia-associated transcription factor expression and significantly attenuated the fraxinol-induced melanin content and intracellular tyrosinase activity. These results suggest that fraxinol enhances melanogenesis via a protein kinase A-mediated mechanism, which may be useful for developing potent melanogenesis stimulators.
Highlights
Melanogenesis is a complex biological and biochemical process involving melanin synthesis [1]
We investigated the effect of fraxinol on melanogenesis and its underlying molecular mechanisms in B16-F10 cells
We investigated the melanogenesis-inducing effect of fraxinol (Figure 1A) in mouse melanoma B16-F10 cells
Summary
Melanogenesis is a complex biological and biochemical process involving melanin synthesis [1]. A recent study reported that multiple pathogenic mechanisms are involved in vitiligo, including genetic changes, oxidative stress, and abnormal innate and adaptive immunities, which lead to melanocyte destruction [6]. This heterogeneity makes the management of vitiligo difficult. Some studies showed that some natural compounds have strong melanogenesis-stimulating effects and suggest that they may be a source for developing anti-vitiligo agents [19,20]. Recent studies have reported that fraxinol has anti-lipase activity, but does not show an inhibitory effect against Helicobacter pylori [25,26]. We investigated the effect of fraxinol on melanogenesis and its underlying molecular mechanisms in B16-F10 cells
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