• Title/Summary/Keyword: Microphthalmia-associated transcription factor

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Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated kinase-mediated inhibition of microphthalmia-associated transcription factor

  • Lee, Seung Jae;Lee, Woo Jin;Chang, Sung Eun;Lee, Ga-Young
    • Journal of Ginseng Research
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    • v.39 no.3
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    • pp.238-242
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    • 2015
  • Background: Panax ginseng has been used to prolong longevity and is believed to be useful for improving skin complexion. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has been demonstrated to possess antioxidative, antitumorigenic, and anti-inflammatory properties. The aim of this study was to examine the ability of G-Rg3 to inhibit melanogenesis. Methods: The effects of G-Rg3 on melanin contents and the protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated. Melanogenesis-regulating signaling molecules such as Akt and extracellular signal-regulated kinase (ERK) were also examined to explore G-Rg3-induced antimelanogenic mechanisms. Results: G-Rg3 was found to significantly inhibit the synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a dose-dependent manner. The activity of cellular tyrosinase and the expression of MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated. PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of melanin synthesis and tyrosinase activity. Conclusion: Taken together, these results showed that G-Rg3 induces the activation of ERK, which accounts for its antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent, adding to the long list of uses of P. ginseng for the enhancement of skin beauty.

Whitening Effect of Salvia miltorrhiza Bunge Water Extract in Human Epidermal Melanocyte (인간 표피 멜라닌 세포에서의 단삼 추출물의 미백효과에 관한 연구)

  • Park, Tae-Soon;Kim, Dong-Hee;Son, Jun-Ho
    • Journal of Applied Biological Chemistry
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    • v.58 no.4
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    • pp.333-338
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    • 2015
  • The objective of this study was to investigate the whitening effect of Salvia miltorrhiza Bunge water extract (SM-W) in human epidermal melanocyte (HEM). Mushroom tyrosinase inhibitory effect of SM-W was approximately 42% at $1,000{\mu}g/mL$. The HEM cellular tyrosinase and melanin synthesis inhibition activity were 26 and 25% at $5{\mu}g/mL$, respectively. Whitening related proteins and mRNAs including tyrosinase, tyrosinase related protein 1 (TRP-1) and TRP-2, and microphthalmia associated transcription factor were reduced by SM-W treatment. In addition, the cAMP expression inhibitory effect of SM-W was decreased by 41% at $5{\mu}g/mL$ concentration. These results indicated that Salvia miltorrhiza Bunge could be used to the possible utilization of functional cosmetic ingredients by confirming whitening activity related with melanin content.

Sageretia thea fruit extracts rich in methyl linoleate and methyl linolenate downregulate melanogenesis via the Akt/GSK3β signaling pathway

  • Ko, Gyeong-A;Shrestha, Sabina;Cho, Somi Kim
    • Nutrition Research and Practice
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    • v.12 no.1
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    • pp.3-12
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    • 2018
  • BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta ($GSK3{\beta}$) signaling pathway, which promotes the reduction of ${\beta}-catenin$. Treatment with the $GSK3{\beta}$ inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

Whitening Effect of Biochanin A (Biochanin A의 미백 효과에 관한 연구)

  • Park, Sung Ha;Kim, A Hyun;Park, Byoung Jun;Kim, Jin Jun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.39 no.4
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    • pp.289-294
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    • 2013
  • To develop a new whitening agent for cosmetics, we investigated the inhibitory effects of biochanin A on melanogenesis. The biochanoin A is an active component in the extracts of Dalbergia odorifera T. Chen. It reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner and decreased to about 48% at a concentration 10 ${\mu}g/mL$. It also inhibited the expression in microphthalmia associated transcription factor (MITF), Tyrosinase, Tyrosinase related protein 1 (Trp-1), and Tyrosinase related protein 2 (Trp-2) in melanocytes. The results suggested that biochanin A has considerable potential as a cosmetics ingredient with a whitening effect.

Inhibitory Effects on Melanin Production of Demethylsuberosin Isolated from Angelica gigas Nakai (참당귀로부터 분리한 Demethylsuberosin의 멜라닌 생성 억제 효과)

  • Kim, You Ah;Park, Sung Ha;Kim, Bo Yun;Kim, A Hyun;Park, Byoung Jun;Kim, Jin Jun
    • Korean Journal of Pharmacognosy
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    • v.45 no.3
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    • pp.209-213
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    • 2014
  • The anti-melanogenic substance was isolated from the root of Angelica gigas Nakai by silica gel column chromatography, preparative HPLC and TLC. As a result of the structure analysis by mass, $^1H$-NMR, and $^{13}C$-NMR spectrometry, the compound was identified as demethylsuberosin. Demethylsuberosin reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner and decreased to about 74% at a concentration $5{\mu}g/ml$. Demethylsuberosin inhibited the expression in microphthalmia associated transcription factor (MITF), tyrosinase, tyrosinase related protein-1 (TRP-1), and tyrosinase related protein-2 (TRP-2) in melanocytes. These results suggest that the whitening activity of demethylsuberosin may be due to the inhibition of the melanin synthesis by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2 expression. Thus, our results provide evidence that demethylsuberosin might be useful as a potential skin-whitening agent.

Inhibitory effects of crude polysaccharide fractions from Annona muricata L. on melanogenesis (그라비올라 잎(Annona muricata L.) 조다당 분획분의 멜라닌 생성 저해 효과)

  • Kim, Yi-Eun;Byun, Eui-Hong
    • Korean Journal of Food Science and Technology
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    • v.51 no.1
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    • pp.52-57
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    • 2019
  • The objective of this study was to evaluate the anti-melanogenic effects of crude polysaccharide fractions from Annona muricata L. (ALP) in 3-isobutyl-1-methylxanthine (IBMX) stimulating hormone-induced mouse B16F10 melanoma cells. The inhibitory effect of ALP on tyrosinase activity was approximately $33.88{\pm}0.79%$ at 5 mg/mL. Additionally, the B16F10 cellular tyrosinase and melanin synthesis inhibition activities by ALP were $54.21{\pm}4.76$ and $56.74{\pm}6.97%$ at $250{\mu}g/mL$, respectively. Similarly, whitening-related protein tyrosinase, tyrosinase-related protein 1 (TRP-1) and TRP-2, and microphthalmia-associated transcription factor (MITF) were reduced by ALP treatment. These results indicated that ALP could be used as a functional cosmetic ingredient after confirming its whitening activity related to melanin content.

Diarylpropionitrile inhibits melanogenesis via protein kinase A/cAMP-response element-binding protein/microphthalmiaassociated transcription factor signaling pathway in α-MSH-stimulated B16F10 melanoma cells

  • Lee, Hyun Jeong;An, Sungkwan;Bae, Seunghee;Lee, Jae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.113-123
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    • 2022
  • Diarylpropionitrile (DPN), a selective agonist for estrogen receptor β (ERβ), has been reported to regulate various hormonal responses through activation of ERβ in tissues including the mammary gland and brain. However, the effect of DPN on melanogenesis independent of ERβ has not been studied. The aim of this study is to examine the possibility of anti-melanogenic effect of DPN and its underlying mechanism. Melanin contents and cellular tyrosinase activity assay indicated that DPN inhibited melanin biosynthesis in alpha-melanocyte stimulating hormone-stimulated B16F10 melanoma cell line. However, DPN had no direct influence on in vitro tyrosinase catalytic activity. On the other hand, 17β-estradiol had no effect on inhibition of melanogenesis, suggesting that the DPN-mediated suppression of melanin production was not related with estrogen signaling pathway. Immunoblotting analysis showed that DPN down-regulated the expression of microphthalmia-associated transcription factor (MITF), a central transcription factor of melanogenesis and its down-stream genes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Also, DPN attenuated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Additionally, DPN suppressed the melanin synthesis in UVB-irradiated HaCaT conditioned media culture system suggesting that DPN has potential as an anti-melanogenic activity in physiological conditions. Collectively, our data show that DPN inhibits melanogenesis via downregulation of PKA/CREB/MITF signaling pathway.

Inhibitory Effects of Novel Hexapeptide on Melanogenesis by Regulating MITF in B16F10 Melanoma Cells (B16F10 멜라닌 세포에서 신규 헥사펩타이드의 MITF 조절을 통한 멜라닌 생성 저해 효과)

  • Lee, Eung Ji;Kim, Jandi;Jeong, Min Kyeong;Lee, Young Min;Chung, Yong Ji;Kim, Eun Mi
    • 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.

Antioxidative Activities and Whitening Effects of Ethyl Acetate Fractions from The Immature Seeds of Abeliophyllum distichum (미선나무 미성숙 종자의 항산화 및 미백 활성)

  • Jang, Tae Won;Park, Jae Ho
    • Journal of Life Science
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    • v.27 no.5
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    • pp.536-544
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    • 2017
  • Abeliophyllum distichum Nakai is deciduous shrubs of flowering plant in Oleaceae. It is important plant resources and consists of one species in the world. Also the endemic plant of A. distichum has been protected and designed endangered plant in Korea. For this reason, study on the immature seeds of A. distichum (ADS) hasn't progressed. In the present study, we evaluated the antioxidant activity and inhibitory effects on proteins and mRNA levels were related in the whitening effect in B16F10 cells. ADS was effective for reaction oxygen species (ROS). ROS causes various diseases such as aging, inflammation, cancer, and etc. Antioxidant properties were evaluated DPPH, ABTS radical scavenging activity and Reducing power. Plants were known that contained phenolic compounds were related in antioxidant activity. Phenolic compounds were phytochemicals commonly named natural polyphenols. These are secondary metabolites of plants involved in the defense against different types of stresses. In results, ADS suppressed the expression and transcription of Tyrosinase, TRP-1, TRP-2, and Microphthalmia-associated transcription factor (MITF). Tyrosinase, tyrosinase-related protein 1 (TRP-1), tyrosinase-related protein 1 (TRP-2) are known to play an important role in melanin biosynthesis. MITF regulated the expression and transcription of Tyrosinase, TRP-1, and TRP-2. In conclusion, ADS was effective in both antioxidant activities and whitening effects. Also, they were associated with the content of phenolic compounds. We suggested that ADS can be use antioxidants and skin-whitening functional cosmetics material derived from natural plant resources.

Identification of polymorphisms in MITF and DCT genes and their associations with plumage colors in Asian duck breeds

  • Sultana, Hasina;Seo, Dongwon;Choi, Nu-Ri;Bhuiyan, Md. Shamsul Alam;Lee, Seung Hwan;Heo, Kang-Nyeong;Lee, Jun-Heon
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.2
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    • pp.180-188
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    • 2018
  • Objective: The aim of this study was to investigate the effect of single nucleotide polymorphisms (SNPs) of the melanogenesis associated transcription factor (MITF) and dopachrome tautomerase (DCT) genes on plumage coloration in Asian native duck breeds. MITF encodes a protein for microphthalmia-associated transcription factor, which regulates the development and function of melanocytes for pigmentation of skin, hair, and eyes. Among the tyrosinase-related family genes, DCT is a pigment cell-specific gene that plays important roles in the melanin synthesis pathway and the expression of skin, feather, and retina color. Methods: Five Asian duck varieties (black Korean native, white Korean native, commercial Peking, Nageswari, and Bangladeshi Deshi white ducks) were investigated to examine the polymorphisms associated with plumage colors. Among previously identified SNPs, three synonymous SNPs and one indel of MITF and nine SNPs in exon regions of DCT were genotyped. The allele frequencies for SNPs of the black and white plumage color populations were estimated and Fisher's exact test was conducted to assess the association between the allele frequencies of these two populations. Results: Two synonymous SNPs (c.114T>G and c.147T>C) and a 14-bp indel (GCTGCAAAC AGATG) in intron 7 of MITF were significantly associated with the black- and white-colored breeds (p<0.001). One non-synonymous SNP [c.938A>G (p.His313Arg)] in DCT, was highly significantly associated (p<0.001) and a synonymous SNP (c.753A>G) was significantly associated (p<0.05) with black and white color plumage in the studied duck populations. Conclusion: The results of this study provide a basis for further investigations of the associations between polymorphisms and plumage color phenotypes in Asian duck breeds.