Abstract
The anti-melanogenic activity of essential oils of Alpinia nantoensis and their bioactive ingredients were investigated in vitro. Treatment with leaf (LEO) and rhizome (REO) essential oils of A. nantoensis, significantly reduced forskolin-induced melanin production followed by down-regulation of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1) expression at both transcriptional and translational levels. Further studies revealed that down-regulation TYR and TRP-1 were caused by LEO/REO-mediated suppression of Microphthalmia-associated transcription factor (MITF), as evidenced by reduced nuclear translocation of MITF. Also, we found that LEO/REO induce the sustained activation of ERK1/2, which facilitate subsequent proteasomal degradation of MITF, as confirmed by that LEO/REO failed to inhibits MITF activity in ERK1/2 inhibitor treated cells. In addition, a significant increase of ubiquitinated MITF was observed after treatment with LEO and REO. Furthermore, the chemical composition of LEO and REO were characterized by gas chromatography-mass spectrometry (GC-MS) resulted that camphor, camphene, α-pinene, β-pinene, isoborneol and D-limonene were the major compounds in both LEO and REO. Further studies revealed that α-pinene and D-limonene were the active components responsible for the anti-melanogenic properties of LEO and REO. Based on the results, this study provided a strong evidence that LEO and REO could be promising natural sources for the development of novel skin-whitening agents for the cosmetic purposes.
Highlights
Melanin is a mixture of pigmented biopolymers synthesized by specialized cells determinant of skin, hair and eye color
microphthalmia transcription factor (MITF) ubiquitination was observed in Leaf Essential Oil (LEO) and Rhizome Essential Oil (REO) or MG132-treated cells when compared with un-treated control cells, while treatment with ERK1/2 inhibitor decreased MITF ubiquitination to below the control level even though in the presence of LEO/REO or MG132. These results demonstrate that LEO and REO treatment leads to ubiquitination and proteasomal degradation of MITF through ERK1/2 activation, which eventually suppress melanin production in melanoma cells
We conclude that leaf and rhizome essential oils obtained from A. nantoensis are able to serve as potential melanogenesis inhibitors
Summary
Melanin is a mixture of pigmented biopolymers synthesized by specialized cells determinant of skin, hair and eye color. Melanin biosynthesis in melanocytes is a complex process involved many factors, including UV irradiation, stem cell factors (SCF), α-melanocyte stimulating hormone (α-MSH), cAMP and transcription factors [2]. MITF, a basic leucine zipper transcription factor directly binds to the promoter regions of melanin production genes and positively regulates their genes, including tyrosinase (TYR), tyrosinase related protein-1 (TRP-1) and dopachrome tautomerase (DCT) [3]. Among these enzymes, tyrosinase is the rate-limiting enzyme and catalyzes the hydroxylation of tyrosinase to
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