Zerumbone, a Tropical Ginger Sesquiterpene of Zingiber officinale Roscoe, Attenuates α-MSH-Induced Melanogenesis in B16F10 Cells

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.

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

“…The used melanoma models are also listed in the Table. Zerumbone B16-F10 [226] where not indicated, EO active components were not available from the cited articles. When referred to in vivo studies, the murine strain used is indicated in brackets.…”

“…Regarding the antimelanogenic effect of EO components, the study of Lin JH's group reported the ability of zerumbrone to decrease melanin accumulation in B16-F10 cells, and to suppress the expression of MITF and its target genes, TYRP1 and TYRP2, after MSH stimulation with a mechanism involving ERK1/2, but not the PKA-CREB signaling pathway [226]. Antimelanogenic activity in the same melanoma model through ubiquitination and proteasomal degradation of MITF, in a ROS/ERK-dependent way, was also reported for phytol [223].…”

Antimelanogenic activities of piperlongumine derived from Piper longum on murine B16F10 melanoma cells in vitro and zebrafish embryos in vivo: its molecular mode of depigmenting action

“…Intracellular tyrosinase activity was determined according to a modified version of a previously described method [26]. Briefly, B16F10 cells were harvested with lysis buffer containing a proteinase inhibitor, and then 20 μl of lysate and 80 μl of 2 mM l-DOPA were added to each well of a 96-well plate and incubated for 2 h at 37 °C.…”

Rice Bran Ash Mineral Extract Increases Pigmentation through the p-ERK Pathway in Zebrafish (Danio rerio)

“…In addition, a variety of other natural extracts for increasing pigmentation have been studied, including Cornus officinalis methanol extract [7], Ardisia crenata extract [8], and Zingiber cassumunar Roxb. [9]. Similarly, many other studies have used organic materials to stimulate pigmentation.…”