• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.6
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• pp.349-355
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• 2019

The anti-inflammatory effects of 4'-O-methylalpinumisoflavone (OMAI) has been reported in recent years. To develop effective and safe skin whitening agents, we investigated the anti-oxidative and melanogenic effects of OMAI isolated from fruit of Maclura tricuspidata Carrière (Cudrania tricuspidata) in macrophage and melanoma cell lines. In our results, OMAI showed effective superoxide scavenging activity and suppressed production of lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) in RAW264.7 cells. In addition, α-melanocyte stimulation hormone (MSH)-induced production of melanin was also reduced by OMAI in B16F10 cells. Finally, OMAI significantly inhibited tyrosinase activity in B16F10 cells. These results suggest that OMAI suppressed melanin production via scavenging reactive oxygen species and inhibition of tyrosinase activity.

• Journal of Life Science
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• v.31 no.7
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• pp.654-661
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• 2021

In this study, in order to isolate excellent whitening agents from fungal cultural broth, various fungi were collected from wild areas in South Korea and then screened for tyrosinase inhibition activity, as tyrosinase is a precursor for the biosynthesis of melanin in regulating skin color. A fungus strain that inhibits tyrosinase activity has been identified and confirmed as Trichoderma viridescens (later renamed T. viridescens SW-1) via ITS sequencing. In T. viridescens SW-1, tyrosinase inhibitory activity was strongest on day three of culture. A 5% culture broth showed a tyrosinase inhibitory activity greater than 90% and exhibited high thermostability on day three. At 10% culture broth, the accumulations of intra- and extracellular melanin were inhibited above 27.1% and 7.5%, respectively. In summary, the physical and functional properties of the tyrosinase inhibitory substances of T. viridescens SW-1 included high levels of inhibition of melanin synthesis and antioxidative activity as well as thermostability. Therefore, we suggest that the whitening substance identified from the cultural broth of T. viridescens SW-1 has potential for application as a functional cosmetic ingredient.

• Natural Product Sciences
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• v.20 no.1
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• pp.33-38
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• 2014

In recent times, the demand for edible medication for the treatment of hyperpigmentation has increased significantly. Therefore, the discovery of a stable, safe and inexpansive antimelanogenic component from natural substances, such as grains, is of particular interest. The levels and activities of some metabolites and/or enzymes can be increased. In the present study, we investigated the antimelanogenic effects of water-soluble extracts from barley (BE), malt (ME) and germinated barley (GBE) in melan-a cells. The inhibitory effects of ME and GBE on melanin production were significantly greater than that of BE. Interestingly, the content of ferulic acid, the proposed active component of barley, was also higher in ME and GBE than in BE by HPLC analysis. Western blot analysis of the expression of melanogenic enzymes in melan-a cells treated with BE, ME or GBE indicated the expression of both tyrosinase and tyrosinase-related protein 2 (TRP-2) significantly decreased after treatment with BE, ME or GBE. These results suggest that besides BE, ME and GBE also inhibit melanin production most likely through suppression of tyrosinase and TRP-2 expression. ME and GBE were more efficacious at inhibiting melanin production than BE was and may also represent potential skin-whitening agents.

• Natural Product Sciences
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• v.22 no.4
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• pp.252-258
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• 2016

Vitex trifolia L. has been used traditionally to treat various illnesses, such as inflammation, headache, migraine, and gastrointestinal infections. We analyzed and evaluated the composition of V. trifolia leaf oil. Based on the results, we isolated abietatriene from V. trifolia leaf oil and investigated the effect of V. trifolia leaf oil and its active compound abietatriene on melanogenesis in B16F10 melanoma cells. They significantly decreased melanin contents and melanogenic factors, such as tyrosinase, TRP-1, TRP-2, and MITF dose-dependently in both protein and mRNA levels. Protein and mRNA expressions were determined by Western blot analysis and quantitative real time RT-PCR. Findings indicate that V. trifolia leaf oil and abietatriene reduce melanogenesis by regulating the expression of melanogenic factors. These results suggest that V. trifolia leaf oil and abietatriene could comprise a useful therapeutic agent for treating hyperpigmentation and used as effective skin-whitening agents.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.287-291
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• 2012

This study investigated the effects of proline-serine (PS) and valine-serine (VS) dipeptides on melanogenesis in Mel-Ab cells. Proline-serine and VS significantly inhibited melanin synthesis in a concentration-dependent manner, though neither dipeptide directly inhibited tyrosinase activity in a cell-free system. Both PS and VS down-regulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. In a follow-up study also described here, the effects of these dipeptides on melanogenesis-related signal transduction were quantified. Specifically, PS and VS induced ERK phosphorylation, though they had no effect on phosphorylation of the cAMP response element binding protein (CREB). These data suggest that PS and VS inhibit melanogenesis through ERK phosphorylation and subsequent down-regulation of MITF and tyrosinase. Properties of these dipeptides are compatible with application as skin-whitening agents.

• Korean Journal of Pharmacognosy
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• v.47 no.1
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• pp.18-23
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• 2016

This study was conducted to investigate the tyrosinase inhibitory and melanin production inhibitory activity of the distilled water extract of Dendropanax morbifera leaf (DMW) and the fermented extract by Lactobacillus plantarum (DMF). DMF was prepared by inoculation of L. plantarum after the extraction procedure with distilled water. Fermentation for 48 hours at $37^{\circ}C$ is the most effective condition in this study. In DPPH radical scavenging ability, $SC_{50}$ values of the fermented DMF was $37.9{\mu}g/ml$ as a result of more effective than DMW extract ($52.6{\mu}g/ml$). Moreover, tyrosinase inhibitory activity of DMF showed higher activity than DMW. In nontoxic concentration range, DMF showed strong melanin production inhibitory effect in ${\alpha}$-melanocyte stimulating hormone-stimulated B16F10 cell. As a result, the fermentation of the distilled water extract of D. morbifera leaf by L. plantarum could be applicable to functional materials production for skin-whitening agents.

• Korean Journal of Food Science and Technology
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• v.44 no.2
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• pp.251-256
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• 2012

Stilbenes are known as antioxidants and some of them demonstrate anti-pigmentation activity. The purpose of the present study was to investigate whether two stilbene compounds produced by biotransformation of the extract of $Morus$ $alba$ root show skin irritation and sensitization. In skin irritation test, 1% oxyresveratrol (OXY), and 5% OXY, and 1% oxyresveratrol-3-$O$-glucoside (OXY-3) showed a P.I.I score of 0, 0.04, and 0, respectively. Accordingly, the two stilbenes were evaluated to be virtually 'non-irritant' materials. In a skin sensitization study by GPMT, 1% OXY, 5% OXY, and 1% OXY-3 did not cause edema and erythema at 24 h and 48 h after topical application and exhibited a sensitization score of 0 and a rate of 0%. Consequently, it was confirmed that OXY and OXY-3 had no contact allergic sensitization in GPMT. Therefore, OXY and OXY-3 might be potential candidates as skin-whitening agents without posing any serious side effects.

• Molecules and Cells
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• v.44 no.10
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• pp.736-745
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• 2021

Although various marine ingredients have been exploited for the development of cosmetic products, no previous study has examined the potential of seaweed extracellular vesicles (EV) in such applications. Our results revealed that EV from Codium fragile and Sargassum fusiforme effectively decreased α-MSH-mediated melanin synthesis in MNT-1 human melanoma cells, associated with downregulation of MITF (microphthalmia-associated transcription factor), tyrosinase and TRP1 (tyrosinase-related proteins 1). The most effective inhibitory concentrations of EV were 250 ㎍/ml for S. fusiforme and 25 ㎍/ml for C. fragile, without affecting the viability of MNT-1 cells. Both EV reduced melanin synthesis in the epidermal basal layer of a three-dimensional model of human epidermis. Moreover, the application of the prototype cream containing C. fragile EV (final 5 ㎍/ml) yielded 1.31% improvement in skin brightness in a clinical trial. Together, these results suggest that EV from C. fragile and S. fusiforme reduce melanin synthesis and may be potential therapeutic and/or supplementary whitening agents.

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

• Food Science and Preservation
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• v.23 no.4
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• pp.585-590
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• 2016

In this study, the antioxidant and tyrosinase inhibitory activities of aqueous ethanolic extract from the immature fruits of Malus pumila cv. Fuji were evaluated. The antioxidant capacities of the extract was investigated employing radical scavenging assays using DPPH and $ABTS^+$ radicals. The skin-whitening effect of M. pumila cv. Fuji extract was tested using mushroom tyrosinase assay. In addition, the total phenolic content was measured by a spectrophotometric analysis. All tested samples showed a dose-dependent radical scavenging and tyrosinase inhibitory activities. Among the tested samples, the ethyl acetate (EtOAc)-soluble portion from the immature fruits of M. pumila cv. Fuji was showed the significant DPPH and $ABTS^+$ radicals scavenging activities. Also, the tyrosinase inhibitory activity of the ethyl acetate (EtOAc)-soluble portion from immature apples was higher than other solvent-soluble portion. These results suggest that unripe fruits of M. pumila cv. Fuji could be considered as a new valuable source of natural antioxidant and skin-whitening agents. Systematic investigation of immature fruits of Malus pumila cv. Fuji will be performed for the further development of its biological properties.