• Journal of Life Science
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• v.31 no.8
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• pp.719-728
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• 2021

Melanin pigments are abundantly distributed in mammalian skin, hair, eyes, and nervous system. Under normal physiological conditions, melanin protects the skin against various environmental stresses and acts as a physiological redox buffer to maintain homeostasis. However, abnormal melanin accumulation results in various hyperpigmentation conditions, such as chloasma, freckles, senile lentigo, and inflammatory pigmentation. Tyrosinase, a copper-containing enzyme, plays an important role in the regulation of the melanin pigment biosynthetic pathway. Although several whitening agents based on tyrosinase inhibition have been developed, their side effects, such as allergies, DNA damage, mutagenesis, and cytotoxicity of melanocytes, limit their applications. In this study, we synthesized 4-chromanone derivatives (MHY compounds) and investigated their ability to inhibit tyrosinase activity. Of these compounds, (E)-3-(4-hydroxybenzylidene)chroman-4-one (MHY1294) more potently inhibited the enzymatic activity of tyrosinase (IC₅₀ = 5.1±0.86 μM) than kojic acid (14.3±1.43 μM), a representative tyrosinase inhibitor. In addition, MHY1294 showed competitive inhibitory action at the catalytic site of tyrosinase and had greater binding affinity at this site than kojic acid. Furthermore, MHY1294 effectively inhibited α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis and intracellular tyrosinase activity in B16F10 melanoma cells. The results of the present study indicate that MHY1294 may be considered as a candidate pharmacological agent and cosmetic whitening ingredient.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.433-441
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• 2013

In this study, the anti-oxidative, anti-inflammatory, anti-melanogenic activities of Endlicheria anomala (Nees) Mez methanol extract (EAME) were evaluated by use of in vitro assays and cell culture model systems. The results revealed that EAME scavenges various radicals such as 1,1-diphenyl-2-picryl hydrazyl hydrogen peroxide induced reactive oxygen species, and lipopolysaccharide induced nitric oxide. Furthermore, EAME induced the expression of anti-oxidative enzymes such as heme oxygenase 1, thioredoxin reductase 1, NAD(P)H dehydrogenase 1, and their upstream transcription factor, nuclear factor-E2-related factor 2. Moreover, EAME inhibited in vitro DOPA oxidation and 3-isobutyl-1-methylxanthine induced melanogenesis in B16F10 cells. Its anti-melanogenic activity will have originated from the inhibition of tyrosinase enzyme activity and melanogenesis related protein expression. Taken together, these results provide the important new insight that E. anomala possesses various biological activities such as anti-oxidative, anti-inflammatory, and anti-melanogenic. Therefore, it might be utilized as a promising material in the fields of nutraceuticals and cosmetics.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.33 no.1 s.60
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• pp.53-60
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• 2007

(6R)-5,6,7,8-tetrahydrobiopterin ($6-BH_4$) cofactor is essential for various process, and is present in probably every cell or tissue of higher organism. $6-BH_4$ is required lot various enzyme activities, and for less defined functions at the cellular level. And it is well known about the antioxidant effects as a non-protein compound. Recently, scientists proposed another roles for $6-BH_4$ in melanogenesis. $6-BH_4$ is a well known tyrosinase inhibitor. In this study, we found that methyl-$BH_4$ and $6-BH_4$ have antioxidant activities and inhibitory activity for melanin synthesis. These pterin compounds were not toxic in HaCaT and B16F10 cells and showed scavenging activity against DPPH radicals. We also showed that pterin compounds decreased protein levels of tyrosinase and TRP-1. In a clinical test, pterin compounds showed the significant skin whiteining effect after treatment for 3 weeks. Furthermore pterin compounds significantly suppressed the UVB-induced expression of $PGE_2$ and IL-6 genes induced UVB In HaCaT and inhibited UVB-induced melanogenesis in B16F10 cells. These results showed the effect of pterin compounds as a cosmeceutical ingredient.

• Korean Journal of Plant Resources
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• v.34 no.4
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• pp.368-376
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• 2021

This study was to investigate the Taraxinic acid from Taraxacum coreanum on tyrosinase activity and melanogenesis. In B16BL6 cell, Taraxinic acid did not show cytotoxicity even at concentrations of up to 100 ㎍/mL. In addition, tyrosinase inhibitory activity and melanogenesis inhibitory activity were confirmed by stimulation with α-melanocyte stimulating hormone (α-MSH) in the presence of taraxinic acid. Taraxinic acid was added to cells at concentrations of 10, 50 and 100 ㎍/mL and treated for 48 hours to confirm tyrosinase inhibitory activity and melanin production. The tyrosinase inhibitory activity increased in proportion to the amount of the sample, and showed an inhibitory activity of about 54.5% at a concentration of 50 ㎍/mL. Melanin production decreased in proportion to the sample amount, and it was about 62.2% at the concentration of 10 ㎍/mL. From the above results, it was found that Taraxinic acid had higher tyrosinase activity and melanin synthesis inhibitory activity in melanocyte than arbutin. The results suggest that Taraxinic acid can be utilized in natural whitening cosmetics.

• Journal of Life Science
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• v.30 no.12
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• pp.1033-1041
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• 2020

Many people of all ages wish to have lighter skin for cosmetic reasons, and natural products attract more attention than chemically synthesized compounds. Uncaria rhynchophylla is widely used in Asia as a traditional herbal medicine. In order to find novel skin whitening agents, the present study evaluated the antioxidant activity and potential tyrosinase-inhibiting properties of U. rhynchophylla. Specifically, this study analyzed the antioxidant capacity of a 70% ethanolic extract of U. rhynchophylla as well as its effects on tyrosinase activity and melanin synthesis. Total mRNA levels were examined using reverse transcription polymerase chain reaction. The results revealed that U. rhynchophylla extracts exhibit great antioxidant capacity and significant levels of polyphenol and flavonoid compounds. U. rhynchophylla extracts can also powerfully inhibit tyrosinase activity. This same capacity was observed in melanoma B16F10 cells; that is, U. rhynchophylla extracts suppressed intracellular tyrosinase activity and reduced the amount of melanin in treated cells. In addition, a 1 mg/ml concentration of U. rhynchophylla extract significantly reduced the mRNA expression levels of tyrosinase. U. rhynchophylla extracts decrease tyrosinase and inhibit melanogenesis in B16F10 cells. This finding suggests that U. rhynchophylla has great potential as a natural whitening agent in skincare products.

• 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.

• Korean Journal of Medicinal Crop Science
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• v.17 no.4
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• pp.293-300
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• 2009

This study was carried out to investigate the effect of Cinnamomum camphora on melanogenesis. The MeOH extract of Cinnamomum camphora inhibited mushroom tyrosinase activity in dose-dependent manner. Moreover, it significantly suppressed the melanin production in melan-a cells at the concentration of $100{\mu}/m{\ell}$. The MeOH extract was partitioned with ethyl acetate, n-butanol and water. Among them, the BuOH soluble fraction exhibited significant inhibitory effect on mushroom tyrosinase. In addition, the BuOH soluble fraction reduced the melanin production in melan-a cells. But, the BuOH soluble fraction had less inhibition effects on melan-a cell originated tyrosinase. So, it was performed western blotting for melanogenic proteins (tyrosinase, tyrosinase-related protein (TRP-2)) using melan-a cells. The BuOH soluble fraction inhibited the protein expression of tyrosinase at the concentration of $100{\mu}/m{\ell}$. The results suggested that the BuOH soluble fraction of C. camphora might be a potent inhibitor of melanin biosynthesis in melan-a cells.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.218-224
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• 2018

Background: Compound K (CK) is a ginsenoside, a metabolite of Panax ginseng. There is interest both in increasing skin health and antiaging using natural skin care products. In this study, we explored the possibility of using CK as a cosmetic ingredient. Methods: To assess the antiaging effect of CK, RT-PCR was performed, and expression levels of matrix metalloproteinase-1, cyclooxygenase-2, and type I collagen were measured under UVB irradiation conditions. The skin hydrating effect of CK was tested by RT-PCR, and its regulation was explored through immunoblotting. Melanin content, melanin secretion, and tyrosinase activity assays were performed. Results: CK treatment reduced the production of matrix metalloproteinase-1 and cyclooxygenase-2 in UVB irradiated NIH3T3 cells and recovered type I collagen expression level. Expression of skin hydrating factors-filaggrin, transglutaminase, and hyaluronic acid synthases-1 and -2-were augmented by CK and were modulated through the inhibitor of ${\kappa}B{\alpha}$, c-Jun N-terminal kinase, or extracellular signal-regulated kinases pathway. In the melanogenic response, CK did not regulate tyrosinase activity and melanin secretion, but increased melanin content in B16F10 cells was observed. Conclusion: Our data showed that CK has antiaging and hydrating effects. We suggest that CK could be used in cosmetic products to protect the skin from UVB rays and increase skin moisture level.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.81-88
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• 2006

Sphingolipid metabolites regulate many aspects of cell proliferation, differentiation, and apoptosis. In the present study, we have assessed the effects of the novel phytosphingosine derivative, N-acetylphytospingosine (NAPS), on the depigmentation of murine B16F10 melanoma cells, and have also attempted to identify the possible signaling pathway involved, in comparison with $C_{2}-ceramide$. NAPS and $C_{2}-ceramide$ both inhibited the growth of the B16F10 cells in a dose-dependent manner. Melanin content and tyrosinase activity were significantly reduced in response to treatment with NAPS and $C_{2}-ceramide$ at concentrations in a range between $1-5\;{\mu}M$. However, the levels of tyrosinase mRNA, as well as the levels of tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2) genes and the level of tyrosinase protein remained unaffected by treatment with either NAPS or $C_{2}-ceramide$. We also attempted to determine the signaling pathway exploited by NAPS and $C_{2}-ceramide$. Interestingly, the phosphorylation of Akt/PKB at serine 473 by NAPS was reduced at the 5 minute mark, whereas $C_{2}-ceramide$ induced the phosphorylation of Akt/PKB at serine 473. Finally, Akt/PKB activity in the NAPS-treated cells was elevated in comparison with the untreated cells. LY294002, a specific PI3-K inhibitor which is located upstream of Akt/PKB, inhibited the phosphorylation of Akt/PKB, but induced an increase in melanin synthesis. These results suggest that the activation of Akt/PKB at serine 473 is related with the suppression of melanin production in the B16F10 mouse melanoma cells. Therefore, the mechanisms exploited by NAPS and $C_{2}-ceramide$ responsible for the depigmentation of B16F10 cells were concluded to involve the inhibition of melanosomal tyrosinase activity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.1
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• pp.41-52
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• 2015

Objective : This study investigated the inhibitory mechanism of the hypopigmentating effects on ethanol extract of Rosae rugosae Flos (ERR) that has not yet been examined. Methods : We analyzed the anti-melanogenic effects of ethanol extracts from Rosae rugosae Flos by tyrosinase activity, melanin contents. We also examined protein expression levels of tyrosinase, TRP-1, TRP-2, MITF and ERK by western blot analysis in melanoma cells. Results : In this investigation, ERR effectively reduced ${\alpha}$-MSH-stimulated melanin synthesis by suppressing expression of tyrosinase and tyrosinase-related protein-1 (TRP-1). On the other hand, the expression of tyrosinase-related protein-2 (TRP-2) were not affected by treatment with ERR. ERR inhibited the expression of microphthalmia-associated transcription factor (MITF) as a key transcription factor for tyrosinase expression regulating melanogenesis. The upstream signaling pathway including cAMP response element-binding protein (CREB) and MAPKs were also inhibited by ERR. Pretreatment with PD98059, ERK inhibitor, attenuated the inhibitory effect of ERR on ${\alpha}$-MSH-induced tyrosinase activity. Conclusions : Our study suggested that the anti-melanogenic activity of ERR is correlated with the suppression of tyrosinase gene through CREB/MITF/ERK pathway.