• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.110-110
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• 2022

Scrophularia koraiensis Nakai (S. koraiensis) has used its roots as traditional herbal medicine. Some research is reported to be effective in allergic inflammation and osteoporosis. In a present study, we conducted to investigate the bioactivity of the ethanol extract of S. koraiensis (ESK) on the inhibition of melanogenesis and the apoptosis of melanocytes. We analyzed Harpagoside of ESK by using LCMS and HPLC-PDA and investigated the regulation of ESK on reactive oxygen species. Also, the expressions of melanin synthesis-related factors and apoptosis-related factors were confirmed. As a result, the quantification results of quercetin and rutin in ESK were 77.2 and 7.4 mg/g. IC₅₀ on DPPH and ABTS radical scavenging activity is 33.1 and 9.5 ug/mL. ESK attenuated not only the expression of tyrosinase, TYRP-1, TYRP-2, and MITF in melanogenesis. It is thought that ESK may be effective in the inhibition of melanogenesis through MAPK cell signaling pathway in melanocytes. These study results suggest that ESK has the ability to inhibit melanin production and induce apoptosis.

• Journal of Life Science
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• v.19 no.3
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• pp.384-389
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• 2009

This study was carried out to elucidate the relation between expression levels of three melanin synthesis genes (Tyrosinase, Tyrosinase-related protein 1 and Dopachrome tautomerase) according to the Melanocortin-1 receptor genotypes with coat color patterns in Hanwoo cattle, Jeju black cattle and Holsteins. Using real-time semiquantitative reverse transcription-PCR assay (RT-PCR), the expression levels of these three genes were analyzed in skin tissues from four representative coat colored areas: yellowish-brown from MC1R e/e Hanwoo, wild type black from $E^+/E^+$ Jeju black cattle (JBC), and dominant black and white pied regions from $E^D/E^D$ Holstein. The TYR, TYRP1 and DCT genes showed higher expression levels of 4.5, 2.3 and 2.5 times higher in the black skin area of Holsteins than those of from JBC, respectively (p<0.001). In addition, the expression levels of these three genes from JBC were significantly higher than those from Hanwoo cattle (p<0.001). These results show that coat color phenotypes in Hanwoo cattle, JBC and Holsteins is directly correlated with TRY, TYRP1 and DCT transcription levels, which probably reflected involvement with MC1R genotypes; e/e in Hanwoo, $E^+/E^+$ in JBC and $E^D/E^D$ in Holsteins. Consequently, this study suggested that the status of MC1R protein may not only induce the transcription activities of a series of TYR and its related genes responsible for melanin synthesis, but also determine the levels of total melanin contents in bovine skin.

• Animal Bioscience
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• v.37 no.4
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• pp.567-575
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• 2024

Objective: This study aimed to identify genes regulated by cyclin dependent kinases 5 (CDK5) that participate in hair pigmentation in mice. Methods: The mRNA expression profiles of skin samples from CDK5-knockdown mice were constructed using high-throughput RNA sequencing and compared with those of wild-type mice. Results: In total, 8,002 known genes were differentially expressed between CDK5-knockdown and wild-type mice. Of these, 3,658 were upregulated and 4,344 were downregulated in the skin of CDK5-knockdown mice. An additional 318 previously unknown genes were also differentially expressed, with 171 downregulated and 147 upregulated genes in the skin of CDK5-knockdown mice. Of the known genes expressed in mouse skin, 80 were associated with hair color, with 61 showing lower expression and 19 exhibiting higher expression in skin of CDK5-knockdown mice. Importantly, the expression of the tyrosinase-related protein 1 (TYRP1) and the calcium signaling pathway were also found to be regulated by CDK5, suggesting that pigmentation is regulated by CDK5 via the calcium signaling pathway and TYRP1. Conclusion: The transcriptome profiles obtained from the skin of CDK5-knockdown mice compared to wild-type mice provide a valuable resource to help understand the mechanism by which CDK5 regulates melanogenesis in mice and other animals.

• Journal of Microbiology and Biotechnology
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• v.30 no.8
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• pp.1184-1194
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• 2020

Melanin is a major factor that darkens skin color as one of the defense systems to prevent the harmful effects of UV light. However, darkened skin from the localized or systemic accumulation of melanin is viewed in many cultures as an esthetic problem. Consequentially, searching for anti-melanogenic agents from natural sources is very popular worldwide. Previous screening of fermented rice products, obtained from various rice cultivars fermented with different sources of loog-pang (Thai traditional fermentation starter), revealed that the highest ability to reduce the melanin content in B16F10 melanoma cells was from unpolished black rice fermented with a defined starter mixture of microbes isolated from loog-pang E11. The aim of this study was to investigate the mechanism of the fermented unpolished black rice (FUBR) on the inhibition of melanogenesis in B16F10 melanoma cells. The strongest reduction of cellular melanin content was found in the FUBR sap (FUBRS). The melanin reduction activity was consistent with the significant decrease in the intracellular tyrosinase activity. The FUBRS showed no cytotoxic effect to B16F10 melanoma or Hs68 human fibroblast cell lines. It also significantly reduced the transcript and protein expression levels of tyrosinase, tyrosinase-related protein 1 (TYRP-1), TYRP-2, and microphthalmia-associated transcription factor. Furthermore, it induced a significantly increased level of phosphorylated ERK, p38 and Akt signaling pathways, which likely contributed to the negative regulation of melanogenesis. From these results, a model for the mechanism of FUBRS on melanogenesis inhibition was proposed. Moreover, these results strongly suggested that FUBRS possesses anti-melanogenesis activity with high potential for cosmeceutical application as a skin depigmenting agent.

• Food Science and Preservation
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• v.18 no.6
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• pp.998-1001
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• 2011

Angelica keiskei is a perennial herb belonging to the Umbelliferae family. In this study, the whitening effect of A. keiskei extracts was examined through melanogenesis and tyrosinase inhibitory assays. The ethanol extract (50%) significantly inhibited tyrosinase in a concentration-dependent manner. RT-PCR revealed that the extract exhibited decreased expression of tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and melanocyte-inducing transcription factor. These results suggest that the extract can be used as an ingredient for the development of cosmeceuticals.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.1
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• pp.11-22
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• 2020

In this study, we investigated anti-pigmentation effect of a hexapeptide. The peptide significantly reduced melanin contents and inhibited tyrosinase activity in a dose-dependent manner, in which tyrosinase is a key enzyme in melanogenesis. The peptide also significantly reduced the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and their upstream transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, the peptide suppressed the phosphorylation level of cAMP-response element binding protein (CREB), a transcription factor of MITF, and increased the phosphorylation level of extracellular signal-regulated kinase (ERK), a kinase mediates MITF phosphorylation and proteasomal degradation. The peptide significantly inhibited the expression of Rab27A, Melanophilin, and MyosinVa, the components of motor complex involved in intracellular movement of melanosome. These results suggest that Hexapeptide could be used as an effective whitening agent that has inhibitory effect on melanin production and melanosome transport by regulating expression and degradation of MITF in melanocytes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.107-121
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• 2021

Skin hypopigmentation, which is observed in albinism or vitiligo, occurs when melanin synthesis is decreased by genetic, epigenetic, and other factors. To identify drug candidates that can promote melanin synthesis in cells, we screened an epigenetic modulator library consisting of 141 cell-permeable, small molecule drugs. B16/F10 murine melanoma cells were treated with each drug at 0.1 𝜇M and melanin synthesis and cell viability were subsequently monitored. As a result, (-)-neplanocin A, 3-deazaneplanocin A (DZNep), and DZNep hydrochloride were found to increase cellular melanin synthesis without causing cytotoxicity. Because these three structurally related drugs exhibited similar dose-dependent effects on melanin synthesis and cell viability, DZNep was selected as a representative drug for additional experiments. DZNep increased intracellular melanin content and tyrosinase (TYR) activity. DZNep also induced the expression of TYR, tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT) at the mRNA and protein levels. DZNep also induced the mRNA and protein expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanin synthesis. DZNep is a specific inhibitor of S-adenosylhomocysteine hydrolase and it caused the accumulation of S-adenosylhomocysteine that inhibits histone methyltransferases in cells. This study suggests that melanogenesis can be modulated by targeting S-adenosylhomocysteine hydrolase in certain cellular contexts.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.714-725
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• 2023

Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.4
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• pp.365-372
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• 2022

Cellobiose is a dissacharide constituted by two glucose units joined by a β-('1,4') glycosidic bond that is produced by the decomposition of cellulose. This product exists naturally in plants and has been utilized in different industries as a food sweetener, and as a cosmetic and pharmaceutical material. In this study, the potential of cellobiose as a whitening cosmetic product was evaluated by analyzing autophagy induction and the inhibition of melanin production. A cytotoxicity test conducted in the human melanin-producing cell line MNT-1 with increasing concentrations of cellobiose revealed that this compound did not cause cytotoxicity at 20 mg/mL or less. Based on this, autophagy was firstly evaluated by immunostaining with the autophagy marker microtubule-associated protein 1 light chain 3 (LC3) after treatment with 20 mg/mL of cellobiose. The subsequent confocal microscopy analysis revealed an increase in LC3 puncta, indicating induction of autophagy. In addition, autophagy was further confirmed by western blot analysis, which demonstrated that cellobiose converted LC3-I to LC3- ∏ in a concentration- and time-dependent manners. An analysis of melanin contents after cellobiose treatment at a concentration of 20 mg/mL during 7 days revealed that melanin production was reduced by more than 50%. Additionally, the expression levels of melanogenesis-related proteins TYR and TYRP1 were markedly decreased after cellobiose treatment. Based on these studies, a cosmetic cream formulation containing cellobiose was prepared and the change in formulation was tested for 4 weeks, and it was confirmed that the appearance changed to liquid form at high temperature, but the pH did not change. In conclusion, the present research demonstrated that cellobiose activates autophagy and inhibits melanin production, and showed the potential of this product as a material for whitening cosmetics.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2004.05a
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• pp.172-176
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• 2004

본 연구는 축우의 모색발현을 조절하는 MCIR, MGF 및 TYRP1 3종류의 모색 유전자를 이용하여 한우육 판별기술을 개발하고자 PCR-RFLP 기법으로 이들 모색유전자 좌위의 대립유전자를 검출하고 각 품종 간 RFLP 유전자형 출현빈도를 비교 분석하였다. MCIR 유전자의 RFLP 유전자형 출현빈도에서 한우는 e/e과 E+/e형이 출현되었고 이외의 다른 유전자형의 출현은 전혀 인정되지 않았다. 그러나, Holstein종 젖소는 $E^D/E^D$와 $E^D/e$ 2종류의 유전자형 그리고 Angus종에서는 $E^D/E^D$, $E^D/E^++$ 및 $E^D/e$ 3종류의 유전자형이 각각 출현하여 한우와 이들 두 품종간의 MCIR유전자형 출현빈도에 뚜렷한 차이가 인정되었다. MGF 유전자의 RFLP 유전자형 출현빈도에서 한우는 R/r과 r/r형이 각각 25%와 75%로 rr형의 출현율이 비교적 높았으며 Holstein종과 Angus 종은 R/r형이 100% 출현했으며, Charolais 종은 rr형이 100% 출현하였고 이외의 다른 유전자형은 인정되지 않았으며 Hereford종은 RR형이 80% 그리고 R/r형이 20%의 출현율을 보여 RR형의 출현율이 매우 높아 한우와 Holstein 및 육우 품종간의 MGF 유전자형 출현빈도에 명백한 차이가 인정되었다. 따라서, 소 모색관련 MCIR과 MGF 유전자의 품종 특이적 PCR-RFLP 유전자형은 한우육과 국내산 Hostein 젖소육 및 도입육우 품종을 식별하는데 매우 유용한 DNA marker로 이용될 수 있음이 확인되었다.