• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.3
• /
• pp.249-254
• /
• 2014

The purpose of this study is to characterize the effects of KHG26792 (3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride), a potential skin whitening agent, on melanin synthesis and identify the underlying mechanism of action. Our data showed that KHG26792 significantly reduced melanin synthesis in a dose-dependent manner. Additionally, KHG26792 downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase, the rate-limiting enzyme in melanogenesis, although tyrosinase was not inhibited directly. KHG26792 activated extracellular signal-regulated kinase (ERK), whereas an ERK pathway inhibitor, PD98059, rescued KHG26792-induced hypopigmentation. These results suggest that KHG26792 decreases melanin production via ERK activation. Moreover, the hypopigmentary effects of KHG26792 were confirmed in a pigmented skin equivalent model using Cervi cornus Colla (deer antler glue), in which the color of the pigmented artificial skin became lighter after treatment with KHG26792. In summary, our findings suggest that KHG26792 is a novel skin whitening agent.

• Korean Journal of Medicinal Crop Science
• /
• v.23 no.4
• /
• pp.298-304
• /
• 2015

Dendrobium loddigesii (DL) is a valuable and versatile herbal medicine with the anecdotal claims of anti-oxidant and anti-inflammation. In the present study, we investigated the whitening effects of DL under various conditions with B16F10 melanoma cells. The DL extract inhibited melanin contents and tyrosinase activity in a dose-dependent manner, compared with untreated group. Treatment of the DL extract effectively suppressed the ${\alpha}$-MSH-stimulated melanin formation, tyrosinase activity and dendrite outgrowth. Moreover, the ${\alpha}$-MSH-induced mRNA expressions of tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), microphthalmia-associated transcription factor (MITF) and protein expression of tyrosinase were significantly attenuated by DL treatment. These results indicate that DL may be a great cosmeceutical ingredient for its whitening effects.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.10a
• /
• pp.90-90
• /
• 2019

Hibiscus syriacus exhibited promising potential as a new source of food and colorants containing various anthocyanins. However, the function of anthocyanins from H. syriacus has not been investigated. In the current study, we evaluated whether anthocyanins from the H. syriacus varieties Pulsae and Paektanshim (PS and PTS) inhibit melanin biogenesis. B16F10 cells and zebrafish larvae were exposed to PS and PTS in the presence or absence of ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH), and melanin contents accompanied by its regulating genes and proteins were analyzed. PS and PTS moderately downregulated mushroom tyrosinase activity in vitro, but significantly decreased extracellular and intracellular melanin production in B16F10 cells, and inhibited ${\alpha}$-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. PS and PTS also attenuated pigmentation in ${\alpha}$-MSH-stimulated zebrafish larvae. Furthermore, PS and PTS activated the phosphorylation of extracellular signal-regulated kinase (ERK), whereas PD98059, a specific ERK inhibitor, completely reversed PS- and PTS-mediated anti-melanogenic activity in B16F10 cells and zebrafish larvae, which indicates that PS- and PTS-mediated anti-melanogenic activity is due to ERK activation. Moreover, chromatography data showed that PS and PTS possessed 17 identical anthocyanins as a negative regulator of ERK. These findings suggested that anthocyanins from PS and PTS inhibited melanogenesis in vitro and in vivo by activating the ERK signaling pathway.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2007.11a
• /
• pp.79-92
• /
• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Journal of Life Science
• /
• v.28 no.6
• /
• pp.681-687
• /
• 2018

Recently, several researchers have been developing cosmetics from natural ingredients for skin whitening and anti-aging products. The red sea cucumber (RSC), Apostichopus japonicas, is a species of sea cucumber in the family stichopodiae, which is widely distributed in China, Japan, and Korea. To use Red Sea Cucumber as a cosmetic ingredient, its inhibitory effects on melanogenesis and the anti-aging effects of RSC extracts were investigated. First, a tyrosinase activity assay was performed, which showed that RSC inhibited tyrosinase activity at a concentration of $200{\mu}g/ml$. An MTT assay was carried out to evaluate cell toxicity, and the results showed that RSC extract has no cytotoxicity in HaCaT cells. Furthermore, the mRNA expression levels of tyrosinase, tyrosinase related protein 1 (TRP-1), tyrosinase related protein 2 (TRP-2), microphthalmia-associated transcription factor (MITF), and matrix metalloproteinase (MMPs) genes treated with RSC extract in B16F10 and HaCaT cells decreased. Moreover, a wound-healing assay was performed to identify the cell regeneration effect of RSC extracts. Also, a skin turnover effect was confirmed by creating a three-dimensional cell culture with HaCaT and human fibroblasts. Altogether, the results suggested that Red Sea Cucumber may possess a high ability to induce whitening and anti-wrinkle effects as a cosmeceutical ingredient.

• Journal of Life Science
• /
• v.27 no.4
• /
• pp.423-429
• /
• 2017

Hair color is determined by kind and amount of melanin. Melanocyte mainly synthesizes melanin from L-tyrosine by stimulation of ultra violet. Reactive oxygen species (ROS) play an important role in greying hair. Polygonum multiflorum radix has been reported to inhibit the aging process that black color of hair is turned into grey color. The aim of this study is to investigate the effect of Polygoni multiflorium radix ethanol extract (PMEE) on melanin synthesis related to black hair growth. In anti-oxidant experiment, PMEE decreased DPPH radical and increased reducing power, indicating that PMEE could eliminate ROS involved in greying hair. PMEE decreased cell viability in a dose-dependent manner. Furthermore, the effect of PMEE on the production of melanin was determined by DOPA assay and tyrosinase activity. PMEE increased tyrosinase activity and promoted melanin synthesis. In addition, the expression levels of tyrosinase, tyrosinase related protein-1 (TRP-1), tyrosinase related protein-2 (TRP-2) and microphthalmia-associated transcription factor (MITF), as well as anti-oxidant enzymes such as superoxide dismutase (SOD-3) and catalase were examined using western blot analysis. The expression levels of SOD-3 and catalase were decreased due to the enhanced antioxidant activity of PMEE. In particular, PMEE increased the expression levels of tyrosinase and TRP-2. These results suggest that PMEE could promote melanin synthesis that involved in tuning gray hair into black hair.

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

• Microbiology and Biotechnology Letters
• /
• v.47 no.1
• /
• pp.148-157
• /
• 2019

A 70% ethanol extract of Erigeron annuus (L.) Pers. was investigated for its whitening activity for application as a functional ingredient in cosmetic products. At the E. annuus extract concentration of $100{\mu}g/ml$, the electron-donating ability was found to be 67.83%, the tyrosinase inhibitory effect (related to skin-whitening) was 69%, the elastase inhibitory effect (related to skin-wrinkling) was 69%, and the astringent effect was 80%. The $ABTS^+$ radical-scavenging ability was 87% at the $500{\mu}g/ml$ concentration. In the cell viability test measured on melanoma cells, 96% of the cells treated with $100{\mu}g/ml$ of the extract were viable. According to the western blot results, the protein expression of the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 was decreased by 60.22%, 47.83%, 54.79%, and 67.88%, respectively, at the extract concentration of $100{\mu}g/ml$. The protein expression of phosphorylated extracellular signal regulated kinase (p-ERK) and phosphorylated cAMP response element-binding protein (p-CREB) was decreased with increasing concentrations of the extract. Reverse transcription-polymerase chain reaction of the extract showed that the mRNA expression of MITF, tyrosinase, TRP-1, and TRP-2 was decreased by 86.51%, 85.22%, 74.26%, and 66.66%, respectively, at $100{\mu}g/ml$ extract concentration. The findings suggest that the 70% ethanol extract from E. annuus (L.) Pers. has potential as a cosmeceutical ingredient with whitening effect.

• Journal of Life Science
• /
• v.31 no.3
• /
• pp.305-313
• /
• 2021

This study verified the antioxidant and whitening activities of a Pinus koraiensis extract (PK) and a Hibiscus cannabinus L. extract (HC), and further evaluated the interaction of the extract ingredients when mixed at a 1:1 ratio (PKHC). The electron-donating and ABTS+ radical scavenging activities of the PKHC extract at 1,000 ㎍/ml concentration were 93.7% and 94%, respectively, indicating a higher efficacy than achieved with either extract alone. Measurements of the tyrosinase the activities in response to PK, HC, and PKHC extracts at 1,000 ㎍/ml concentrations showed inhibitions of 40%, 27.5%, and 43%, respectively, confirming a higher efficacy of the mixture due to the synergistic action of the ingredients. The cell toxicity values in melanoma cells treated with PK, HC, and PKHC at 1,000 ㎍/ml concentration were 87.4%, 80.2%, and 98%, confirming a higher viability in cells treated with the mixture due to antagonism. The expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and tyrosinase protein expression determined by Western blotting decreased by 53.9%, 64.8%, 67.3%, and 56.1%, respectively, when PKHC was administered at a concentration of 100 ㎍/ml. Reverse transcription-polymerase chain reaction (RT- PCR) results also showed that PKHC at a concentration of 100 ㎍/ml inhibited the mRNA expression of MITF, TRP-1, TRP-2, and tyrosinase mRNA by 54.4%, 64.9%, 66.6%, and 63.1%, respectively. Taken together, the data confirmed the antioxidant and whitening effect of the PKHC extract and verified the possibility that this extract mixture has great potential as a cosmetic ingredient.

• Korean Journal of Medicinal Crop Science
• /
• v.24 no.1
• /
• pp.38-46
• /
• 2016

Background : The white jelly mushroom (Tremella fuciformis), one of the most popular edible fungi, has medicinal properties. However, the effects of T. fuciformis in skin whitening or anti-wrinkle efficacy has not been defined to date. The aim of the present study was to investigate the effects of T. fuciformis extracts on whitening and anti-wrinkle efficacy in skin cells. Methods and Results :We prepared T. fuciformis extracts with water. The extracts ($80^{\circ}C$) contained 12.11 mg/g polyphenol and 8.54 mg/g flavonoid concentration. T. fuciformis extracts markedly decreased melanin contents and tyrosinase activity in ${\alpha}$-MSH-stimulated melanocytes (B16F10 cells). In addition, the mRNA expression of melanin formation factors, such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were significantly down-regulated in ${\alpha}$-MSH-stimulated melanocyte. Furthermore, T. fuciformis extracts increased the synthesis of type I procollagen and reduced mRNA expression of matrix metalloproteinase 1 (MMP-1) in the human dermal fibroblast (HDFn cells). These data indicated that T. fuciformis extracts induce repression of cellular melanogenesis and protect against wrinkles caused by UVB-stimulated damage. Conclusions : Thus T. fuciformis extracts could be a cosmetic candidate for skin whitening and anti-wrinkle effects.