• Journal of Photoscience
• /
• v.9 no.2
• /
• pp.201-204
• /
• 2002

Epidermal cells produce a panel of antioxidants as well as cytokines after UVB irradiation, which counteract reactive oxygen species, however, how these antioxidants might regulate melanogenesis is unclear. An important constituent of the cellular antioxidant buffering system which controls the redox state of proteins is thioredoxin (TRX), a 13-kD protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biological functions similar to cytokines. TRX suppressed the UVB-induced production and secretion of $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocyte (KC)s. Further, L-cysteine, N-acetyl-cysteine, $\alpha$-tocopheryl ferulate showed suppressive effect on UVB-induced POMC mRNA expression. However, TRX released from UVB-irradiated KCs stimulated melanogenesis by up-regulating MSH receptor expression and its binding activity in melanocyte (MC)s. UVB-induced KC derived cytokines such as IL1, IL6, and ET1 upregulated MSH-receptor binding ability as well as MCl-R mRNA expression in cultured normal human MCs. MCl-R has a tendency to be upregulated by UVB-induced KC-derived cytokines as well as by direct UVB irradiation. These results suggest that antioxidants such as TRX suppresses UVB induction of POMC, but in the case of MCl-R, this gene can be mainly in the trend of upregulation by UVB-induced KC-derived factors including TRX.

• Korean Journal of Veterinary Research
• /
• v.58 no.2
• /
• pp.65-72
• /
• 2018

The present study observed the effects of a green tea (Camellia sinensis) flower extract (GTFE) on melanin synthesis in B16-F10 melanoma cells. GTFE exhibited antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl and inhibited mushroom tyrosinase activity in a dose-dependent manner. Furthermore, GTFE significantly diminished ${\alpha}-melanocyte$ stimulating hormone (${\alpha}-MSH$) stimulated cellular melanin content and tyrosinase activity throughout the concentration range evaluated. Based on RNA sequencing analysis, differential gene expression patterns observed in ${\alpha}-MSH$ stimulated B16-F10 melanoma cells were normalized by the addition of GTFE. In particular, the expression levels of melanoregulin and tyrosinase genes which are key regulating genes in melanin synthesis were up-regulated by 3.5 and 3 fold respectively by ${\alpha}-MSH$, and were normalized to control levels by the addition of GTFE. The results suggest that GTFE inhibits melanin synthesis in ${\alpha}-MSH$ stimulated B16-F10 melanoma cells by normalizing expression of genes that are essential for melanin synthesis. Overall, the results suggest that GTFE could be applied in the development of a whitening agent for the treatment of dermal hyperpigmentation.

• The Korea Journal of Herbology
• /
• v.27 no.4
• /
• pp.73-80
• /
• 2012

Objectives : Under normal condition melanin protects the skin from extracellular stimuli including ultraviolet (UV)-induced oxidative skin damages, but excess production and accumulation of melanin can induce hyperpigmentation causing esthetic problems. Therefore, in this study we tried to search for natural skin whitening materials from marine natural resources. Methods : Water and ethanol extracts of marine natural resources were prepared from Porphyra thalli (PT), Laminariae thallus (LT), Ostreae concha (OC), Sargassum thallus (ST), Undaria thallus (UT), Codium thalli (CT), Enteromorpha thalli (ET), Syngnathoides biaculeatus (SB), and Hippocampus coronatus (Hc). Their effects against UVB and ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH)-induced melanogenesis were investigated based on melanin formation in B16 mouse melanoma cells. The mRNA and protein expression of enzymes involved in the melanogenic process were further examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. Results : Water extract of Ostreae concha (OCW/E) effectively inhibited UVB and ${\alpha}$-MSH-induced melanin production in B16 melanocytes, which seemed to be mediated by inhibition of mRNA expression of tyrosinase and tyrosinase-related protein 1 (TRP-1). In another experiment, ethanol extracts from Porphyra thalli (PTE/E), Laminariae thallus (LTE/E), Sargassum thallus (STE/E), Undaria thallus (UTE/E), Codium thalli (CTE/E), Syngnathoides biaculeatus (SBE/E), and Hippocampus coronatus (HcE/E) significantly suppressed UVB and ${\alpha}$-MSH-induced melanin formation. Furthermore, ethylacetate fraction isolated form LTE/E (LTE/EEt) decreased UVB and ${\alpha}$-MSH-elevated extracellular melanin levels via inhibition of tyrosinase protein expression. Conclutions : These results suggest that marine natural resources such as Porphyra thalli, Laminariae thallus, Ostreae concha, Sargassum thallus, Undaria thallus, Codium thalli, Syngnathoides biaculeatus and Hippocampus coronatus have anti-melanogenic effects, thereby exhibiting high potentials to be utilized as one of the ingredients for the development of new whitening functional cosmetics.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1996.11a
• /
• pp.153-159
• /
• 1996

${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.

• YAKHAK HOEJI
• /
• v.45 no.3
• /
• pp.269-275
• /
• 2001

The inhibitory effect of extract of Atractylodis Rhizoma alba on melanin biogenesis was studied by using B16/F10 melanoma in culture. Atractylodis Rhizoma alba significantly inhibited tyrosinase activity, and melanin contents with or without $\alpha$-MSH and forskolin in vitro. Melanin contents and tyro-sinase activity have decreased in a dose-dependent manner. These results show that extract of Atractylodis Rhizoma alba could be developed as skin whitening components of cosmetics.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.5
• /
• pp.705-711
• /
• 2014

In order to develop a skin-whitening agent, melanin contents and intracellular tyrosinase activity were determined by western blotting. Ethyl acetate fractions of 80% ethanol extracts from lily (Lilium Oriental Hybrid 'Siberia') bulbs (R-EA) inhibited melanin synthesis in a dose-dependent manner in ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH)-treated B16/F10 murine melanoma cells. Intracellular tyrosinase activity and melanin contents were suppressed by 45% and 74%, respectively, in response to treatment with $100{\mu}g/mL$ of R-EA. Examination of protein expression associated with ${\alpha}$-MSH-induced melanogenesis showed that tyrosinase related protein (TRP)-1 was inhibited more strongly than tyrosinase, and these results were correlated with stronger inhibition of melanin synthesis than intracellular tyrosinase activity. Taken together, R-EA containing p-coumaric acid and resveratrol could be used as a hypopigmentation agent through suppression of sustained extracellular signal-regulated kinase (ERK) activation via melanogenic induction.

• IMMUNE NETWORK
• /
• v.2 no.4
• /
• pp.208-216
• /
• 2002

Background: Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity. Key members of the MMR system include MutS${\alpha}$ (comprised of hMSH2 and hMSH6), which can sense and repair single base mismatches and 8-oxoguanine, and MutS${\beta}$ (comprised of hMSH2 and hMSH3), which repairs longer insertion/deletion loops. Methods: To provide further evidence of DNA damage, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells (PBC) of RA patients using specific primer sequences for 5 key microsatellites. Results: Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis (OA) tissue. Western blot analysis of the same tissues for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Western blot analysis demonstrated constitutive expression of hMSH2, 3 and 6 in RA and OA FLS. When FLS were cultured with SNAP, the RA synovial pattern of MMR expression was reproduced (high hMSH3, low hMSH6). Conclusion: Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

• YAKHAK HOEJI
• /
• v.56 no.6
• /
• pp.395-400
• /
• 2012

To investigate the possibility of development as a whitening agent using arctigenin, we measured DPPH assay, NBT/XO assay, intracellular ROS scavenging assay, tyrosinase assay and MSH-induced melanin production in B16 melanoma cells. Arctigenin dose-dependently had anti-oxidant activity in DPPH, NBT/XO and intracellular ROS assay. Although arctigenin did not inhibit purified tyrosinase activity, it dose-dependently inhibited tyrosinase activity and melanin production in B16 melanoma cells stimulated by $1{\mu}M$ ${\alpha}$-MSH. In particular, arctigenin at a concentration $100{\mu}M$ inhibited ${\alpha}$-MSH-stimulated tyrosinase activity and melanin production by $50.9{\pm}2.9%$ and $69.0{\pm}6.5%$ respectively. And typical tyrosinase inhibitor, arbutin, inhibited $57.7{\pm}2.9%$ and $65.1{\pm}5.0%$ respectively. Such an similar inhibitory effect of arctigenin and arbutin in B16 melanoma cells may be due to the inhibition of MSH signal pathway rather than the direct inhibition of tyrosinase. Therefore, these results suggest that arctigenin may be useful for the development as whitening agents.

• Preventive Nutrition and Food Science
• /
• v.21 no.2
• /
• pp.155-159
• /
• 2016

Previous research showed that resveratrol (trans-3,4',5-trihydroxystilbene) and pinostilbene (trans-3-methoxy-4',5-dihydroxystilbene) were able to inhibit tyrosinase directly; however, anti-melanogenic effects of pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene) and resveratrol trimethyl ether (RTE) have not been compared. To investigate the hypopigmentation effects of pterostilbene and RTE, melanin contents and intracellular tyrosinase activity were determined by western blot analysis. Firstly, pterostilbene showed the inhibitory effects on ${\alpha}$-melanocyte stimulating hormone (MSH)-induced melanin synthesis stronger than RTE, resveratrol, and arbutin. Pterostilbene inhibited melanin biosynthesis in a dose-dependent manner in ${\alpha}$-MSH-stimulated B16/F10 murine melanoma cells. Specifically, melanin content and intracellular tyrosinase activity were inhibited by 63% and 58%, respectively, in response to treatment with $10{\mu}m$ of pterostilbene. The results of western blot analysis indicated that pterostilbene induced downregulation of tyrosinase protein expression and suppression of ${\alpha}$-MSH-stimulated melan-A protein expression stronger than RTE or resveratrol. Based on these results, our study suggests that pterostilbene can induce hypopigmentation effects more effectively than resveratrol and RTE, and it functions via downregulation of protein expression associated with hyperpigmentation in ${\alpha}$-MSH-triggered B16/F10 murine melanoma cells.

• Fisheries and Aquatic Sciences
• /
• v.22 no.5
• /
• pp.11.1-11.8
• /
• 2019

Background: In the present study, the skin-whitening effects of a marine-sourced mixture that includes a fucoidanrich extract of Undaria pinnatifida (UPEF), a phlorotannin-rich extract of Ecklonia cava (ECE), and glycosaminoglycans (GAGs) from sea squirt skin were investigated. Methods: The whitening effects of the mixture and its components were evaluated by measuring the inhibition of mushroom tyrosinase and melanin synthesis in alpha-melanocyte-stimulating hormone (${\alpha}$-MSH)-stimulated B16F10 melanoma cells. Results: Each component alone markedly inhibited mushroom tyrosinase in a dose-dependent manner, and in ${\alpha}$-MSH-stimulated B16F10 cells, they inhibited melanin synthesis and were cytotoxic. However, the whitening effects of UPEF, ECE, and GAGs in combination were greater than those of each component alone. A mixture in the ratio of 4:5:1 (UEG-451) showed the strongest activity without cytotoxicity. Further study suggested that UEG-451 inhibits ${\alpha}$-MSH-stimulated melanogenesis in B16F10 cells by downregulating tyrosinase and tyrosinase-related proteins, such as TRP-1 and TRP-2, via the inhibition of MITF expression. Conclusions: These results suggest that mixing the different components at optimum ratios might be an effective way to improve their bioactivities and reduce toxicity and that UEG-451 possesses strong whitening effects that could be used in the cosmetic industry.