• Journal of the Society of Cosmetic Scientists of Korea
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• v.26 no.2
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• pp.41-50
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• 2000

- Biochemical studies show that in the process of mixed melanogenesis, cysteinyldopas are produced first which are next oxidized to give pheomelanin. After all of the cysteine is consumed, eumelanin is then deposited on the preformed pheomelanin. - In vitro and in vivo studies show that tyrosinase activity is the most important factor that regulates the switch of melanogenesis, with higher activities increasing melanogenesis, especially eumelanogenesis. - In culturted melanocytes, the tyrosine to cysteine ratio is critical in determining the eumelanin to pheomelanin ratio. - Our HPLC method to analyze eumelanin and pheomelanin has become a useful tool in the study of melanogenesis regulation. There are many problems to be solved before we fully understand the regulation of melanogenesis. Mutations in mouse models are ideal models for studying the genetic and molecular control of melanogenesis. Even in the mouse models, it is not known how cysteine is excluded from being incorporated into melanins in black and other eumelaninc mice, Conversely, it is not known how cysteine is continuously incorporated into pheomelanin in lethal yellow and recessive yellow mice.

• Biomedical Science Letters
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• v.13 no.4
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• pp.313-317
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• 2007

Melanogenesis refers to the biosynthesis of melanin pigment in melanocytes. Melanogenesis is controlled by the intra- and extracellular environments. In the present study, to develop a new whitening agent, it was investigated the antioxidant activity and the inhibitory effect of Ailanthi Radicis Cortex extract on tyrosinase activity and on melanogenesis in the B16/F1 melanoma cells. The inhibition ratio of tyrosinase activity of ethylacetate fraction from Ailanthi Radicis Cortex was higher than that of arbutin. The ethylacetate fraction showed scavenging activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide anion radicals in a dose dependent manner. The highest inhibitory activity of melanogenesis was also in ethylacetate fraction ($40.0{\pm}5%$ at the concentration of $400{\mu}g/ml$). This study demonstrates that the Ailanthi Radicis Cortex extract might be used to be a potential agent for skin whitening.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.724-729
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• 2001

Melanogenesis is a physiological process resulted in the synthesis of melanin pigments, which has a role in protecting skin front the damaging effect of ultra-violet (UV) radiation. The main aim of the present study was to examine the effect of Ulmus davidiana var. japonica(UL) on Melanogenesis. Cells were cultured in the presence of various concentrations of Ulmus davidiana var. japonica for 48 h, and there were estimated total melanin contents as a final product and activity of tyrosinase, a key enzyme, in Melanogenesis. Among the four solvent extracts tested, EtOAc extract mostly increased tyrosinase activity, And EtOAc extract increased the melanin contents and tyrosinase activity in a dose-dependent manner. Especially It was observed that 100$\mu\textrm{g}$/ml EtOAc extract promotes melanin secretion in B16/F10 melanoma cells by 140% at 48 h treatment and activity of tyrosinase increased by 180% in the presence of same concentration. In conclusion, as for EtOAc extract treatment, there was no effect on the viability of B16/F10 cell, only to stimulate Melanogenesis.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.1-6
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• 2015

Abnormal changes in skin color induce significant cosmetic problems and affect quality of life. There are two groups of abnormal change in skin color; hyperpigmentation and hypopigmentation. Hyperpigmentation, darkening skin color by excessive pigmentation, is a major concern for Asian people with yellowe-brown skin. A variety of hypopigmenting agents have been used, but treating the hyperpigmented condition is still challenging and the results are often discouraging. Panax ginseng has been used traditionally in eastern Asia to treat various diseases, due to its immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Recently, several reports have shown that extract, powder, or some constituents of ginseng could inhibit melanogenesis in vivo or in vitro. The underlying mechanisms of antimelanogenic properties in ginseng or its components include the direct inhibition of key enzymes of melanogenesis, inhibition of transcription factors or signaling pathways involved in melanogenesis, decreasing production of inducers of melanogenesis, and enhancing production of antimelanogenic factor. Although there still remain some controversial issues surrounding the antimelanogenic activity of ginseng, especially in its effect on production of proinflammatory cytokines and nitric oxide, these recent findings suggest that ginseng and its constituents might be potential candidates for novel skin whitening agents.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.485-491
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• 2011

Previously, we have reported that apigenin, a natural flavonoid found in a variety of vegetables and fruits, stimulated melanogenesis through the activation of $K^+-Cl^-$-cotransport (KCC) in B16 melanoma cells. In this study we investigated the possible involvement of reactive oxygen species (ROS) in the mechanism of apigenin-induced melanogenesis in B16 cells. Apigenin elevated intracellular ROS level in a dose-dependent manner. Treatment with various inhibitors of NADPH oxidase, diphenylene iodonium (DPI), apocynin (Apo) and neopterine (NP) significantly inhibited both the generation of ROS and melanogenesis induced by apigenin. In addition these inhibitors profoundly inhibited apigenin-induced $Cl^-$-dependent $K^+$ efflux, a hallmark of KCC activity. However, the apigenin-induced ROS generation was not significantly affected by treatment with a specific KCC inhibitor R-(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]acetic acid (DIOA). These results indicate that the ROS production may be a upstream regulator of the apigenin-induced KCC stimulation, and in turn, melanogenesis in the B16 cells. Taken together, these results suggest that the NADPH oxidase-mediated ROS production may play an important role in the apigenin-induced melanogenesis in B16 cells. These results further suggest that NADPH oxidase may be a good target for the management of hyperpigmentation disorders.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.89-96
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• 2023

Uric acid produced by guanine deaminase (GDA) is involved in photoaging and hyperpigmentation. Reactive oxygen species (ROS) generated by uric acid plays a role in photoaging. However, the mechanism by which uric acid stimulates melanogenesis in GDA-overexpressing keratinocytes is unclear. Keratinocyte-derived paracrine factors have been identified as important mechanisms of ultraviolet-induced melanogenesis. Therefore, the role of paracrine melanogenic growth factors in GDA-induced hypermelanosis mediated by uric acid was examined. The relationships between ROS and these growth factors were examined. Primary cultured normal keratinocytes overexpressed with wild type or mutant GDA and those treated with xanthine or uric acid in the presence or absence of allopurinol, H₂O₂, or N-acetylcysteine (NAC) were used in this study. Intracellular and extracellular bFGF and SCF levels were increased in keratinocytes by wild type, but not by loss-of-function mutants of GDA overexpression. Culture supernatants from GDA-overexpressing keratinocytes stimulated melanogenesis, which was restored by anti-bFGF and anti-SCF antibodies. Allopurinol treatment reduced the expression levels of bFGF and SCF in both GDA-overexpressing and normal keratinocytes exposed to exogenous xanthine; the exogenous uric acid increased their expression levels. H₂O₂-stimulated tyrosinase expression and melanogenesis were restored by NAC pretreatment. However, H₂O₂ or NAC did not upregulate or downregulate bFGF or SCF, respectively. Overall, uric acid could be involved in melanogenesis induced by GDA overexpression in keratinocytes via bFGF and SCF upregulation not via ROS generation.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.207-212
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• 2014

Skin hyperpigmentation is one of the most common skin disorders caused by abnormal melanogenesis. The mechanism and key factors at play are not fully understood. Previous reports have indicated that cystamine (CTM) inhibits melanin synthesis, though its molecular mechanism in melanogenesis remains unclear. In the present study, we investigated the effect of CTM on melanin production using ELISA reader and the expression of proteins involved in melanogenesis by Western blotting, and examined the involvement of transglutaminase-2 (Tgase-2) in SK-MEL-2 human melanoma cells by gene silencing. In the results, CTM dose-dependently suppressed melanin production and dendrite extension in a-MSH-induced melanogenesis of SK-MEL-2 human melanoma cells. CTM also suppressed a-MSH-induced chemotactic migration as well as the expressions of melanogenesis factors TRP-1, TRP-2 and MITF in a-MSH-treated SK-MEL-2 cells. Meanwhile, gene silencing of Tgase-2 suppressed dendrite extension and the expressions of TRP-1 and TRP-2 in a-MSH-treated SK-MEL-2 cells. Overall, these findings suggested that CTM suppresses a-MSH-induced melanogenesis via Tgase-2 inhibition and that therefore, Tgase-2 might be a new target in hyperpigmentation disorder therapy.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.885-888
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• 2002

Four diarylheptanoids, (5R)-1,7-bis (3,4-dihydroxyphenyl)-heptane-5-O-$\beta$-D-glucoside (1), (5R)-1,7-bis (3,4-dihydroxyphenyl)-heptane-5-ol (2), oregonin (3), hirsutanonol (4), were isolated from the bark of Alnus hirsuta Turcz and its inhibitory effects on melanogenesis by measuring the melanin level and tyrosinase activity in B16 melanoma cell were examined. Melanin level and tyrosinase activity were reduced to 75 to 85% by addition of diarylheptanoids to incubation medium of the melanoma cell. On the other hand, melanin level and tyrosinase activity were reduced to 13 to 43% by the addition of diarylheptanoids to incubation medium of the melanoma cell treated with melanogenesis stimulator, $\alpha$-MSH and forskolin. These melanogenesis inhibitory effects were significantly different compared with control.

• Journal of Microbiology and Biotechnology
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• v.22 no.6
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• pp.814-817
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• 2012

In the continued search for melanogenesis inhibitors from microbial metabolites, we found that the culture broth of Clitocybe sp. MKACC 53267 inhibited melanogenesis in B16F10 melanoma cells. The active component was purified by solvent extraction, silica gel chromatography, Sephadex LH-20 column chromatography, and finally by preparative HPLC. Its structure was determined as 5-pentyl-2-furaldehyde on the basis of the UV, NMR, and MS spectroscopic analysis. The 5-pentyl-2-furaldehyde potently inhibited melanogenesis in B16F10 cells with an $IC_{50}$ value of 8.4 ${\mu}g/ml$, without cytotoxicity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.1
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• pp.100-111
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• 2003

Recently many efforts were focused to understand the mechanical insights of melanogenesis to develop the agents for hyper-pigmentation and hypo-pigmentation. In the melanin biosynthetic pathway, tyrosinase is the rate limiting enzyme, and ${\alpha}$-melanocyte stimulating hormone(MSH) or cAMP-elevating agents stimulate melanogenesis and enhance the melanin synthesis and the tyrosinase activity. The author has analyzed the effects of Rhizoma Bletillae on the basal melanogenic activities of B16 mouse melanoma cells. Rhizoma Bletillae alone markedly suppressed melanin content and tyrosinase activity in a dose-dependent manner. Pretreatment of the cells with Rhizoma Bletillae. The decrease in the tyrosinase activity was paralled by a decrease in the abundance of tyrosinase protein and tyrosinase promoter activity. These results suggest that Rhizoma Bletillae inhibits melanogenesis of B16 melanoma cells via suppression of tyrosinase activity.