• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.15-26
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• 2021

Peptides are short chain of amino acids linked by peptide bonds. They are widely used as effective and biocompatible active ingredients in cosmetic industry. In this study, we developed novel peptide mixture and identified its anti-pigmentation effect on melanocytes and keratinocytes. Our results revealed that peptide mixture inhibited melanosome biogenesis through the regulation of microphthalmia-associated transcription factor, a key factor of melanogenesis in melanocytes. And we observed that peptide mixture inhibited melanosome uptake through the reduction of protease-activated receptor 2, a phagocytosis-related receptor in keratinocytes. Furthermore, peptide mixture activated autophagy system resulting in degradation of transferred melanosomes in keratinocytes. The anti-pigmentation effect of multi-targeting peptide mixture was assessed in a human skin equivalent model (MelanoDerm). Melanin contents in epidermal layer were significantly decreased by topical treatment of peptide mixture, suggesting that it can be applied as a novel cosmetics material having a whitening function.

• Journal of Photoscience
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• v.9 no.2
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• pp.213-216
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• 2002

Skin pigmentation, also known as complexion coloration, results from the biosynthesis of melanin within the melanocytes of the Stratum basalum and the subsequent transfer, translocation, and degradation of this pigment to, in, and by the neighboring keratinocytes respectively, Melanins are produced and retained in melanosomes synthesized in the cell body that are translocated along the dendrites using microtubules via motor proteins. Melanosomes are eventually captured and retained at the tips of dendrites by attachment to the peripherally localized actin. Melanosomes reaching the dendritic tips are transferred to keratinocytes, primarily via phagocytosis of released melanosomes by keratinocytes. Molecules responsible for cell/cell recognition and interaction that regulate transfer are being identified. Some of these putative mediators appear to be affected by ultraviolet radiation. After the keratinocytes receive melanosomes, the granules are distributed individually or as clusters in dark versus light skin respectively. These melanosomes are then aggregated over the nucleus for photoprotection ofkeratinocyte DNA and eventually degraded.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.300-304
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• 2019

• Journal of the Society of Cosmetic Scientists of Korea
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• v.41 no.3
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• pp.243-252
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• 2015

Melanosome, the pigment granule in melanocyte, determines the color of skin when it moves into the keratinocyte. Inhibition of melanosome transfer from melanocyte to keratinocyte results in skin depigmentation. Protease activated receptor-2 (PAR-2) is involved in signal transduction systems via cell membrane and increases the melasome transfer when it is activated by cleavage of their extracellular amino acid sequence by trypsin or by a peptide such as SLIGKV. Here, we showed that lobaric acid inhibited PAR-2 activation and affected the mobilization of $Ca2^+$. The uptake of fluorescent microspheres and isolated melanosomes from melan-a melanocytes to keratinocytes induced by SLIGKV were inhibited by lobaric acid. Also, confocal microscopy studies illustrated a decreased melanosome transfer to keratinocytes in melanocyte-keratinocyte co-culture system by lobaric acid. In addition, lobaric acid induced visible skin lightening effect in human skin tissue culture model, melanoderm$^{(R)}$. Our data suggest that lobaric acid could be an effective skin lightening agent that works via regulation of phagocytic activity of keratinocytes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.28 no.3
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• pp.7-39
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• 2002

The extensive variation in human cutaneous pigmentation is mainly due to differences in the rate of melanin synthesis by epidermal melanocytes, the relative amounts of eumelanin and pheomelanin synthesized, and the manner and rate of transfer of melanosomes from melanocytes to keratinocytes. Pigmentation is a complex trait that is regulated genetically and environmentally. One gene that has been receiving a lot of attention is the gene for the melanocortin 1 receptor The extensive polymorphism of this gene in human populations suggests its significance in the diversity of pigmentation. Exposure to solar ultraviolet radiation (UV) results in increased synthesis of a variety of growth factors, cytokines and hormones, and in modulation of their receptors in the epidermis. Knowledge about the regulation of pigmentation has led to strategies for clinical treatment of hyperpigmented skin lesions. Three main strategies are: 1) the use of chemicals that interfere with the melanin synthetic pathway, 2) the design of peptides or peptide-mimetics based on the structure of hormones that regulate eumelanin synthesis, and 3) the use of agents that reduce melanosome transfer from melanocytes to keratinocytes. All three strategies are expected to induce hypopigmentation, by inhibiting total melanin synthesis, eumelanin production, or the epidermal melanin unit, respectively.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.231-239
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• 2024

Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm^TM. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.203-211
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• 2022

Melanogenesis is the production of melanin from tyrosine by a series of enzyme-catalyzed reactions, in which tyrosinase and DOPA oxidase play key roles. The melanin content in the skin determines skin pigmentation. Abnormalities in skin pigmentation lead to various skin pigmentation disorders. Recent research has shown that the expression of EMP2 is much lower in melanoma than in normal melanocytes, but its role in melanogenesis has not yet been elucidated. Therefore, we investigated the role of EMP2 in the melanogenesis of MNT1 human melanoma cells. We examined TRP-1, TRP-2, and TYR expression levels during melanogenesis in MNT1 melanoma cells by gene silencing of EMP2. Western blot and RT-PCR results confirmed that the expression levels of TYR and TRP-2 were decreased when EMP2 expression was knocked down by EMP2 siRNA in MNT1 cells, and these changes were reversed when EMP2 was overexpressed. We verified the EMP2 gene was knocked out of the cell line (EMP2 CRISPR/Cas9) by using a CRISPR/Cas9 system and found that the expression levels of TRP-2 and TYR were significantly lower in the EMP2 CRISPR/Cas9 cell lines. Loss of EMP2 also reduced migration and invasion of MNT1 melanoma cells. In addition, the melanosome transfer from the melanocytes to keratinocytes in the EMP2 KO cells cocultured with keratinocytes was reduced compared to the cells in the control coculture group. In conclusion, these results suggest that EMP2 is involved in melanogenesis via the regulation of TRP-2 expression.