• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.1
• /
• pp.29-34
• /
• 2015

Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did not do so directly. Western blot analysis indicated that fucoidan downregulated microphthalmia-associated transcription factor and reduced tyrosinase protein expression. Further investigation showed that fucoidan activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a possible mechanism for the inhibition of melanin synthesis. Treatment with PD98059, a specific ERK inhibitor, resulted in the recovery of melanin production. Taken together, these findings suggest that fucoidan inhibits melanogenesis via ERK phosphorylation.

• Journal of Ginseng Research
• /
• v.39 no.3
• /
• pp.238-242
• /
• 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.

• 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.

• Proceedings of the KAIS Fall Conference
• /
• 2012.05a
• /
• pp.182-186
• /
• 2012

human tyrosinase (hTyr) catalyzes first and the rate limiting step in the synthesis of polymerized pigment, melanin which determines skin, hair and eye colors. Mutation of hTyr often brings about decrease of melanin production and further albinism. Meanwhile, a number of cosmetic companies providing skincare products for woman in Asia-Pacific region have tried to develop inhibitors to bright skin color for several decades. In this study, we built a 3D structure by comparative modeling technique based on the crystal structure of tyrosinase from bacillus megaterium as a template to serve structural information of hTyr. According to our model and sequence analysis of type 3 copper protein family proteins, two copper atoms of active site located deep inside are coordinated with six strictly conserved histidine residues coming from four-helix-bundle. Cavity which accommodates substrates was like funnel shape of which entrance was wide and expose to solvent. In addition, protein-substrate and protein-inhibitor complex were modeled with the guide of van der waals surface generated by in house software. Our model suggested that only phenol group or its analogs can fill the binding site near nuclear copper center because inside of binding site has narrow shape relatively. In conclusion, the results of this study may provide helpful information for designing and screening new anti-melanogensis agents.

• Microbiology and Biotechnology Letters
• /
• v.37 no.1
• /
• pp.49-54
• /
• 2009

Rhapontin is the glycosylated stilbene compound, and comprising major component of rhubarb root extract. Rhapontin has been used as a raw material of skin-whitening cosmetics in Korea. Rhapontigenin, the aglycone of rhapontin, has been suggested to be more active than its glycosylated form. Therefore, the rhubarb root extract was treated with commercial enzyme, Pectinex to remove glycosylated moiety of rhapontin and rhapontigenin was prepared. The resulting material was analysed and identified as rhapontigenin by proton NMR and MALDI-Mass. Rhapontigenin exhibited tyrosinase inhibitory activity with an $IC_{50}$ of $126.72{\mu}g/mL$. The tyrosinase inhibitory activity of rhapontigenin was six times higher than that of rhapontin. In melanin biosynthesis inhibition assay using Streptomyces bikiniensis, rhapontigenin showed wider inhibition zone than that of rhapontin. From these results, we expect that rhapontigenin has stronger skin whitening effect than rhapontin and has advantages in cosmetic industry.

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

• Journal of Applied Biological Chemistry
• /
• v.63 no.1
• /
• pp.89-93
• /
• 2020

In this study, the efficacy of melanoma cell B16F10 was investigated using the Korean native plant Oplismenus undulatifolius (OU). First, the cell viability of the extract was more than 90% when treated with 15 ㎍/mL of phenolics from OU. The results showed that melanin biosynthesis and cellular tyrosinase synthesis were inhibited by treatment with α-melanocyte-stimulating hormone-stimulated mouse melanoma cell B16F10 at a concentration of 15 ㎍/mL of phenolics for cell-line efficacy. The expression of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and microphthalmia transcription factor (MITF) protein was confirmed by western blot to investigate the effect of phenolics from OU on melanin biosynthesis. When treated with phenolics from OU 15 ㎍/mL, tyrosinase, TRP-1, TRP-2, and MITF decreased the protein expression level. In particular, tyrosinase, TRP-1, and MITF inhibited the production amount to a level similar to that of the non-treated normal group, indicating that the effect was excellent. Therefore, phenolics from OU acts as an inhibitor of tyrosinase, TRP-1, TRP-2, and its transcription factor MITF, and participates in melanin biosynthesis mechanism. These results suggested the potential for development as a material.

• Korean Journal of Food Science and Technology
• /
• v.33 no.6
• /
• pp.760-763
• /
• 2001

To develop a functional beverage from Korean cherry (Prunus tomentosa Thunberg), inhibition effect of ethanol extract and juice of the korean cherry on melanin systhesis and tyrosinase activity in vitro was investigated. Inhibition ratio of tyrosinase activity increased as the concentration of solid of korean cherry juice increased, and inhibition affect was high in initiation step of enzyme reaction and then gradually decreased. Inhibition ratio of tyrosinase activity was high in the 70% (v/v) ethanol extract of the cherry and the highest in the ethyl acetate fraction of the 70% (v/v) ethanol extract. Ultimatly, the amounts of functional matter (melanin synthesis inhibitor) in the cherry was highest in ethyl acetate fraction of the ethanol extract.

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

• Bulletin of the Korean Chemical Society
• /
• v.31 no.7
• /
• pp.2036-2038
• /
• 2010