Abstract
Zerumbone (ZER), an active constituent of the Zingiberaceae family, has been shown to exhibit several biological activities, such as anti-inflammatory, anti-allergic, anti-microbial, and anti-cancer; however, it has not been studied for anti-melanogenic properties. In the present study, we demonstrate that ZER and Zingiber officinale (ZO) extract significantly attenuate melanin accumulation in α-melanocyte-stimulating hormone (α-MSH)-stimulated mouse melanogenic B16F10 cells. Further, to elucidate the molecular mechanism by which ZER suppresses melanin accumulation, we analyzed the expression of melanogenesis-associated transcription factor, microphthalmia-associated transcription factor (MITF), and its target genes, such as tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2), in B16F10 cells that are stimulated by α-MSH. Here, we found that ZER inhibits the MITF-mediated expression of melanogenic genes upon α-MSH stimulation. Additionally, cells treated with different concentrations of zerumbone and ZO showed increased extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, which are involved in the degradation mechanism of MITF. Pharmacological inhibition of ERK1/2 using U0126 sufficiently reversed the anti-melanogenic effect of ZER, suggesting that increased phosphorylation of ERK1/2 is required for its anti-melanogenic activity. Taken together, these results suggest that ZER and ZO extract can be used as active ingredients in skin-whitening cosmetics because of their anti-melanogenic effect.
Highlights
Melanogenesis, the production of melanin by epidermal melanocytes, is stimulated by the α-melanocyte stimulating hormone (α-MSH) that is secreted from keratinocytes upon exposure to ultraviolet (UV) radiation [1,2]
In order to study the anti-melanogenic effect of zerumbone (ZER), we initially evaluated its cytotoxicity in both B16F10 and HaCaT cells
We investigated the inhibitory effects of ZER on α-melanocytes stimulating hormone (α-MSH)-induced melanin accumulation and secretion in B16F10 cells
Summary
Melanogenesis, the production of melanin by epidermal melanocytes, is stimulated by the α-melanocyte stimulating hormone (α-MSH) that is secreted from keratinocytes upon exposure to ultraviolet (UV) radiation [1,2]. Microphthalmia-associated transcription factor (MITF), which is a melanogenic transcription factor, is activated through the cAMP-PKA-CREB (cyclic adenosine monophosphate-protein kinase A-cAMP response element binding protein) signaling pathway upon α-MSH stimulation via melanocortin 1 receptor (MC1R) in cytoplasmic membranes of epidermal melanocytes [4]. Several chemicals, such as forskolin and IBMX (3-isobutyl-1-methylxanthine), are known to activate the cAMP-PKA-CREB signaling pathway, leading to the induction of melanogenesis [5]. U0126, a selective ERK1/2 pathway inhibitor, has been reported to increase MITF expression and tyrosinase activity, leading to melanin production [6]. Mature melanin is transported from epidermal melanocytes into the cytoplasm of the basal keratinocytes to protect cells from UV radiation [2]
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