• Journal of Life Science
• /
• v.32 no.5
• /
• pp.331-339
• /
• 2022

Melanin is a pigment produced by melanocytes to protect the skin from external stimuli, mainly ultraviolet (UV) rays. However, abnormal and excessive production of melanin causes hyperpigmentation disorders, such as freckles, age spots, and discoloration. Natural cosmeceuticals are a new trend for treating or preventing hyperpigmentation due to fewer side effects and biocompatibility. In this context, the current study focused on Cnidium japonicum, a halophyte with several uses in folk medicine, to evaluate its potential as a skin-whitening agent. The effect of C. japonicum extract (CJE) on melanin production was analyzed in melanogenesis-stimulated B16F10 melanoma cells. The results showed that CJE successfully inhibited the oxidation of tyrosine and L-DOPA by tyrosinase and subsequently decreased the production of the key enzymes responsible for melanin production: tyrosinase, tyrosinase-related protein-1, and protein-2. This effect was confirmed by decreased intracellular and extracellular melanin levels in B16F10 melanoma cells after CJE treatment. Further experiments to elucidate the action mechanism revealed that CJE treatment suppressed melanin production by inhibiting the activation of glycogen synthase kinase 3 β (GSKβ)/β-catenin and protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathways, which are the upstream activators of melanogenesis. In conclusion, the present study suggests that C. japonicum is a potential natural source of bioactive substances for the development of novel cosmeceuticals that can act against hyperpigmentation.

• Korean Journal of Ichthyology
• /
• v.21 no.3
• /
• pp.208-213
• /
• 2009

Histological examination of an individual of the Korean slender gudgeon Squalidus gracilis majimae having cutaneous albinism produced rarely in the wild was made and compared with a normal individual. The external body of the albino was colorless, differing from the normal individual, which has dense brownish black spots over its body surface. To make it clear through histological study, we observed eight skin regions: dorsal, lateral, ventral, upper caudal peduncle, lower caudal peduncle, dorsal fin, anal fin, and the eyes. These regional skins were the same in fundamental structure between albinic and normal gudgeon, but there were significant differences in distribution and development of pigment cells (melanins). In the normal gudgeon, the pigment cells were well developed over the regional skins except on the skin from the ventral region. However, it was confirmed in the albino that the pigment cells were vestigial over the upper regions of the eye and body but absent in the ventral region, lower caudal peduncle, and anal fin.

• Applied Microscopy
• /
• v.27 no.1
• /
• pp.71-86
• /
• 1997

The regeneration and differentiation of the cutaneous pigment system in the goldfish, Carassius auratus during the wound healing process were studied with high magnification electron microscope. The cutaneous pigment cells of the normal tissues were composed of three kinds of dermal chromatophores-xanthophores, leucoiphores and melanophores. While xanthophores contain two kinds of pigment granules-pterinosomes and carotenoid vesicles, leucophores and melanophores contain amorphous pigment granules (leucosomes) and oval shaped electron dense melanin pigment granules (melanosomes) respectively. After injury, primary wound healing responses being carried out by migration of epidermal cells and hemocytes spreading over the wound surface at the day of wounding. And at the time of primary wound closure, 5 to 7 days after wounding, rER rich cells-presumably common precursors of dermal chromatophores-immigrated into the wound area. First redifferentiated chromatophores appeared 3 weeks after wounding. Pigment granules of the chromatophores were emerged from the cytoplasmic Golgi complex via rough endoplasmic reticulum. Pinocytotic vesicles which associated with accumulation of pigment material, appeared only at the inner surface of the chromatophores adhering to the rER rich cells, characteristically. The differentiation of each chromatophore in addition to integumental wound repair were accomplished within 4 weeks after wounding at most cases, however the total numbers and densities of these repaired chromatophores still primitive state. Moreover, It has been revealed that complete repair of chromatophores at wounded tissues from burns requirs more than 3 months in normal environment.

• Archives of Plastic Surgery
• /
• v.38 no.6
• /
• pp.725-732
• /
• 2011

Purpose: Skin grafting is one of the most commonly used methods in reconstructive plastic surgery field, but complications such as color change, contracture or hypertrophy are common problems. However, pathophysiology of the color change after skin graft is not yet determined and no animal model is established. Methods: Full thickness skin grafts were performed on the dorsum of C57BL/6 mice. Serial chronological gross inspection for color change and pigmentation were examined. Melanin pigments were traced by Fontana-Masson staining and semi-quantitative analysis was performed. In addition, immunohistochemical staining of S-100, Micropthalmia related Transcription Factor (MITF) and Melan-A antibodies were also performed to observe melanocytes and their changes. Results: After skin graft, color change and pigment spots were observed in the graft. Fontana-Masson staining showed melanin pigments in the epidermal and dermal layers in all mice. Immunohistochemistry staining to S-100, MITF, Melan-A antibodies showed melanocytes at the basal layer of epidermis and dermis. Conclusion: In conclusion, we have established an animal model for skin pigmentation after skin graft. We believe this study may be useful in understanding of the behavior of melanocytes after skin graft.

• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.1
• /
• pp.53-61
• /
• 2018

Ethyl linoleate is an unsaturated fatty acid used in many cosmetics for its various attributes, such as antibacterial and anti-inflammatory properties and clinically proven to be an effective anti-acne agent. In this study, we investigated the effect of ethyl linoleate on the melanogenesis and the mechanism underlying its action on melanogenesis in B16F10 murine melanoma cells. Our results revealed that ethyl linoleate significantly inhibited melanin content and intracellular tyrosinase activity in ${\alpha}$-MSH-induced B16F10 cells, but it did not directly inhibit activity of mushroom tyrosinase. Ethyl linoleate inhibited the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein 1 (TRP1) in governing melanin pigment synthesis. We observed that ethyl linoleate inhibited phosphorylation of Akt and glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) and reduced the level of ${\beta}-catenin$, suggesting that ethyl linoleate inhibits melanogenesis through $Akt/GSK3{\beta}/{\beta}-catenin$ signal pathway. Therefore, we propose that ethyl linoleate may be useful as a safe whitening agent in cosmetic and a potential therapeutic agent for reducing skin hyperpigmentation in clinics.

• Preventive Nutrition and Food Science
• /
• v.10 no.3
• /
• pp.244-250
• /
• 2005

The copper-containing enzyme, tyrosinase, catalyzes the oxidation of tyrosine into dihydroxy phenylalanine (DOPA) and subsequently DOPAquinone. It is responsible, not only for the pigment melanin biosynthesis in human skin, but also for browning in foods. In the present study, tyrosinase inhibitory and antioxidant activities of Korean mistletoe extract and its fractions were investigated. As a result, both water and methanol (MeOn) extracts inhibited the tyrosinase activity. Among the fractions, the fraction eluted with $95\%$ MeOn significantly inhibited the tyrosinase activity. The fraction was further purified, and the purified fraction C strongly inhibited the enzyme activity up to $92\%$. In addition, water and methanol extracts exerted radical scavenging effects. The fractions eluted with $70\%\;MeOn\;and\;95\%$ Me on showed high radical scavenging activities. In conclusion, these results suggest that Korean mistletoe extract and its fractions might be useful for the treatment of various dermatological disorders such as epidermal hyperpigmentation and for improving food quality.

• BMB Reports
• /
• v.46 no.7
• /
• pp.364-369
• /
• 2013

Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia-associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITF-siRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2007.11a
• /
• pp.129-139
• /
• 2007

Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. The ideal depigmenting compound should have a potent. rapid and selective bleaching effect on hyperactivated melanocytes, carry no short- or long-term side-effects and lead to a permanent removal of undesired pigment. acting at one or more steps of the pigmentation process. Depigmentation can be achieved by regulating (i) the transcription and activity of tyrosinase, tyrosinase related protein-1 (TRP-1), tyrosinase related protein-2 (TRP-2), and/or peroxidase; (ii) the uptake and distribution of melanosomes in recipient keratinocytes and (iii) melanin and melanosome degradation and turnover of pigmented keratinocytes. One of the interesting point for development of skin whitening agent is Mitf(Microphthalmia-associated transcription factor). Mitf belongs to the basic helix-loop-helix-zip family of trabscription factors and it is crucial as it regulates both melanocyte proliferation as well as melanogenesis and is the major regulator of tyrosinase and the related enzymes (TRPs), as well as many melanosome structural proteins such as pMel17. Recently, we developed MITF-down-regulating agents from natural and synthetic sources, which have anti-melanogenic effect on in vitro and in vivo. We suggested that potent MITF-down regulating agents might be used for skin whitening cosmeceuticals.

• Korean Journal of Veterinary Research
• /
• v.46 no.3
• /
• pp.275-278
• /
• 2006

A 7-month-old brown pig with a discoid and pedunculate mass measuring $14.0{\times}12.5{\times}2.5cm$ on the skin of the right shoulder was noted at the slaughter house in Jeju. The surface of mass approximately $7{\times}4cm$ was interfaced with skin. The color of mass with firm consistency was mainly black and partially white on cut surface. Histopathologically, numerous unencapsulated endocrine-like cellular nodules of epithelioid cell type with abundant intracytoplasmic black pigment, melanin, were occupied in dermis and subcutis. Most of nodules in deep dermis were surrounded by lightly pigmented spindle cells and loose fibrous tissues. Mitotic figures were infrequently observed. The overlying epidermis was hyperplastic due to the down-growth of rete peg. Based on the gross and histopathologic findings, this case was diagnosed as cutaneous melanoma. In our best knowledge, this is the first case of swine cutaneous melanoma in Korea.