Melanogenesis-inducing effect of cirsimaritin through increases in microphthalmia-associated transcription factor and tyrosinase expression.

Hyo Kim,Ik-Soo Lee,Byung-Yoon Cha,Jong-Sang Kim,Jin Kim,Je-Tae Woo,Il Kim,Yin Dong

doi:10.3390/ijms16048772

Abstract

The melanin-inducing properties of cirsimaritin were investigated in murine B16F10 cells. Cirsimaritin is an active flavone with methoxy groups, which is isolated from the branches of Lithocarpus dealbatus. Tyrosinase activity and melanin content in murine B16F10 melanoma cells were increased by cirsimaritin in a dose-dependent manner. Western blot analysis revealed that tyrosinase, tyrosinase-related protein (TRP) 1, TRP2 protein levels were enhanced after treatment with cirsimaritin for 48 h. Cirsimaritin also upregulated the expression of microphthalmia-associated transcription factor (MITF) after 24 h of treatment. Furthermore, cirsimaritin induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner after treatment for 15 min. The cirsimaritin-mediated increase of tyrosinase activity was significantly attenuated by H89, a cAMP-dependent protein kinase A inhibitor. These findings indicate that cirsimaritin stimulates melanogenesis in B16F10 cells by activation of CREB as well as upregulation of MITF and tyrosinase expression, which was activated by cAMP signaling. Finally, the melanogenic effect of cirsimaritin was confirmed in human epidermal melanocytes. These results support the putative application of cirsimaritin in ultraviolet photoprotection and hair coloration treatments.

Highlights

Production of melanin in skin, hair, and eyes is required for photoprotection against ultraviolet (UV) irradiation, embryonic development, detoxification, and cosmetic coloration [1]
To clarify the mechanism of cirsimaritin in melanin synthesis, we examined the phosphorylation of cAMP responsive element-binding protein (CREB), which is involved in tyrosinase activation/expression through upregulation of microphthalmia-associated transcription factor (MITF) gene expression
Because activation of CREB is required for cyclic adenosine monophosphate (cAMP) responsiveness of the MITF promoter [25,26], we explored the involvement of the cAMP/protein kinase A (PKA) pathway in cirsimaritin-regulated melanogenesis

Summary

Introduction

Production of melanin in skin, hair, and eyes is required for photoprotection against ultraviolet (UV) irradiation, embryonic development, detoxification, and cosmetic coloration [1]. Melanins are synthesized in melanosomes of melanocytes through the activity of various enzymes including tyrosinase, tyrosinase-related protein (TRP) 1 and TRP2 ( known as dopachrome tautomerase). Tyrosinase catalyzes the o-hydroxylation of tyrosine (monophenol) to 3,4-dihydroxyphenylalanine (L-DOPA; diphenol) and the subsequent oxidation of DOPA to dopaquinone. TRP1 oxidizes 5,6-dihydroxyindole-2-carboxylic acid to indole-5,6-quinone-2-carboxylic acid in mice, but not in humans. TRP2 isomerizes dopachrome to 5,6-dihydroxyindole-2-carboxylic acid [2]. Elevated levels of intracellular cyclic adenosine monophosphate (cAMP) allow activation of protein kinase A (PKA) that phosphorylates cAMP responsive element-binding protein (CREB)

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Results

Conclusion