• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.87-94
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• 2021

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation. Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+]i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at -60 mV and ORAI1 current by 97% ± 1% at -120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

• Archives of Plastic Surgery
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• v.34 no.5
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• pp.587-592
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• 2007

Purpose: In case of postburn flexion contracture of the fingers, skin graft, geometrical relaxation techniques, local flap, and free flap have been used. Among these procedures, full-thickness skin grafts from the inguinal area are widely used to reconstruct a postburn flexion contracture in the fingers. But there are many esthetic and functional problems in this procedure. Especially, hyperpigmentation of the skin-grafted fingers poses a troublesome problem, particularly in the patients who have dark colored skin. To solve the problem, we have used pulp graft which was harvested from the lateral aspect of great toe. In the present study, we report pulp graft, with which we have obtained a good result in the treatment of postburn flexion contracture of the fingers. Methods: Between September of 2004 and August of 2006, great toe pulp graft was performed to 20 sites of 15 patients. After release of the postburn flexion contracture using Z-plasty, the composite tissue (pulp) harvested from the lateral aspect of great toe was grafted on the raw surface. Moisture dressing with ointment and foam dressing material was performed. Stratum corneum of the graft got stripped off in two to four weeks after pulp graft. The color of the pulp graft was slightly reddish, then it became similar to the adjacent tissue. Results: There was complete take in all the patients who were treated with pulp graft. Great toe pulp graft provided similar color and texture to the adjacent skin, high rate of graft take, and left only a minimal scar at donor site. Conclusion: Thick keratin layer and inelastic nature of the pulp make this type of the graft much easier and simpler, and ensure a better take. Pulp graft is useful method for the reconstruction of the postburn flexion contracture in fingers.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.27 no.1
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• pp.119-131
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• 2001

Exposure of the human skin to UV-light can cause sun-tanning, photoaging and even photo-carcinogenesis. Melanin is important in protecting the skin against UV damage, but excessive or uneven melanin production can lead to the formation of freckles and aged spot. Control of hyperpigmentation is becoming even more important as aged population continues to grow. These needs led us to develop effective and safe depigmenting-agent, kojyl 3-aminopropyl phosphate (kojyl-APPA), called Whitegen. The development of whitegen was based on the fact that phosphate group of 3-aminopropyl phosphate can make kojic acid more compatible to the skin membrane and more stable. Instability of kojic acid has been a problem in cosmetic use. The insertion of phosphoester group has been recognized as a powerful tool to improve such physical properties as solubility and stability, because the phosphodiester residue is well characterized as a non-toxic moiety, having a high affinity for cell membranes. Kojyl-APPA showed no tyrosinase inhibition effect compared to kojic acid in vitro, but showed tyrosinase inhibition effect in situ. It means that kojyl-APPA is converted to kojic acid enzymatically in cells. Kojyl-APPA showed the inhibitory activity on melanin synthesis in mouse melanoma and normal humal melnaocytes and also showed long-lasting stability in comparison with its original form (kojic acid). Kojyl-APPA showed depigmenting effects when applied to UVB-induced hyperpigmentated region of guinea pig skin. Based on these results, kojyl 3-aminopropyl phosphate can be used as a safe and effective ingredient for the brightness and cleanness of skin.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.431-437
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• 2014

Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation, such as arbutin, hydroquinone, and kojic acid, are only moderately effective. But, their use is limited by side effects. As part of an effort to overcome the limitations, we developed resveratrol-enriched rice (RR) using genetic engineering technique. Each of resveratrol and rice has been reported to produce anti-melanogenic effects. Therefore, we hypothesized that RR would show more anti-melanogenic effects than those of resveratrol or rice alone. Anti-melanogenic effect of RR was done by using melan-a mouse melanocytes. The depigmenting efficacy was then observed following topical application of the RR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs. Treatment with RR extract resulted a $21.4{\pm}0.7%$ decrease in tyrosinase expression at melan-a cells. Colorimetric analysis showed a significantly lower depigmenting value by day 9 following treatment with RR in UVB-irradiated guinea pigs the dorsal skin (p<0.01), indicating that RR produced a depigmentation effect. By staining with Fontana-Masson stain, we found that the RR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group. RR was associated with reduction in the levels of microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase and tyrosinase-related protein (TRP-2) expression, leading to inhibit epidermal melanin production by western blot analysis. This study suggests that the resveratrol-enriched rice may be a promising candidate in regulating skin pigmentation with UVB exposure.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1349-1360
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• 2019

Chronic exposure to ultraviolet (UV) radiation, regarded as a major cause of extrinsic aging or photoaging characterized by wrinkle formation and skin dehydration, exerts adverse effects on skin by causing the overproduction of reactive oxygen species. Agastache rugosa Kuntze, known as Korean mint, possesses a wide spectrum of biological properties including anti-oxidation, anti-inflammation, and anti-atherosclerosis. Previous studies have reported that A. rugosa protected human keratinocytes against UVB irradiation by restoring the anti-oxidant defense system. However, the anti-photoaging effect of A. rugosa extract (ARE) in animal models has not yet been evaluated. ARE was orally administered to hairless mice at doses of 100 or 250 mg/kg/day along with UVB exposure for 12 weeks. ARE histologically improved UVB-induced wrinkle formation, epidermal thickening, erythema, and hyperpigmentation. In addition, ARE recovered skin moisture by improving skin hydration and transepidermal water loss (TEWL). Along with this, ARE increased hyaluronic acid levels by upregulating HA synthase genes. ARE markedly increased the density of collagen and the amounts of hydroxypoline via two pathways. First, ARE significantly downregulated the mRNA expression of matrix metalloproteinases responsible for collagen degradation by inactivating the mitogen-activated protein kinase/activator protein 1 pathway. Second, ARE stimulated the transforming growth factor beta/Smad signaling, consequently raising the mRNA levels of collagen-related genes. In addition, ARE not only increased the mRNA expression of anti-oxidant enzymes but also decreased inflammatory cytokines by blocking the protein expression of nuclear factor kappa B. Collectively, our findings suggest that A. rugosa may be a potential preventive and therapeutic agent for photoaging.

• Journal of Life Science
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• v.29 no.11
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• pp.1200-1207
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• 2019

Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and $20{\mu}m$. Cell viability assays confirmed that doses of loganin up to $20{\mu}m$ were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with ${\alpha}-MSH$ and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by ${\alpha}-MSH$ and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.

• Journal of Sasang Constitutional Medicine
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• v.27 no.2
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• pp.240-253
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• 2015

Objectives The aim of this study was to investigate the effects of GalGunSeungGi-Tang (GST) on allergic contact dermatitis (ACD) induced by 2,4-dintrochlorobenzone (DNCB) Methods In this study, The changes of body weight, ear weight, ear thickness, spleen weight, dorsum skin thickness, symptom score by eyesight, histological finding, proliferation rates of splenocyte in vitro and in vivo are investigated to check effects of GST. The mice are divided into four group; Normal (naive mice), Control (DW administered), GST-L (GST 500mg/Kg/day administered), GST-H (GST 1,000mg/Kg/day administered). Results GST inhibited weight of ear significantly (P < 0.05) and also thickness (P < 0.01). In addition, There are significant decrease in thickness of dorsum skin and proliferation rates of splenocyte in vivo in GST administered group. Finally, GST reduced symptom score and hyperkeratosis, hyperpigmentation, increase of granulocyte and parakeratosis in histological finding. Conclusions These results suggest that GST can decrease symptoms of ACD.

• Journal of Microbiology and Biotechnology
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• v.18 no.5
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• pp.874-879
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• 2008

Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be reduced by treatment with depigmenting agents. The methanol extract of Lespedeza cyrtobotrya $M_{IQ}$ showed inhibitory activity against mushroom tyrosinase. The active compound was purified from the methanol extract of L. cyrtobotrya, followed by several chromatographic methods, and identified as dalbergioidin (DBG) by spectroscopic methods. The results showed that DBG exhibited tyrosinase inhibitory activity with an $IC_{50}$ of $20\;{\mu}M$. The kinetic analysis of tyrosinase inhibition revealed that DBG acted as a noncompetitive inhibitor. In addition, DBG showed a melanin biosynthesis inhibition zone in the culture plate of Streptomyces bikiniensis that has commonly been used as an indicator organism. Furthermore, $27\;{\mu}M$ DBG decreased more than 50% of melanin contents on the pigmentation using the immortalized mouse melanocyte, melan-a cell.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.104-117
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• 2002

Objective : The aim of this study was to investigate the skin-whitening effect of Kakamseosiokyong-san Method : We investigated that the extracts of Kakamseosiokyong-san inhibit activity of tyrosinase, the enzyme which converts 3-(3,4-dihydroxyphenyl)alanine to dopachrom in the biosynthetic process of melanin. the UV absorbance of the extracts in the UV - A region and UV - B region was measured by UV scanning. the effect of extracts on cell viability and melanin production in cultured B16 mouse melanoma cells was measured, and cytoprotective effects of extracts on PC12 cells injured by hydrogen peroxide was measured by MTT assay Results: The extracts of Kakamseosiokyong-san inhibited activity of tyrosinase. The extracts not only showed inhibitory effects on melanin production in cultured B16 mouse melanoma cells, but also exhibited cytoprotective effects on PC12 cells injured by hydrogen peroxide, but did not showed an absorbance in the UV - A region and UV - B region. Conclusion: These results suggest that Kakamseosiokyong-san inhibit melanin biosynthesis which is involved in hyperpigmentation and could be used as a whitening agent for the skin.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.281.1-281.1
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• 2002

Psoralen(7H-Furo［3.2-g］ ［1］benzopyran-7-one) and angelicin(2-Oxo-[2H]- furo[2.3-h]-1-benzopyran) are angular furocoumarin with diverse photobiological effects. They are major components of Psoralea corylifolia L.(破古紙). Psoralea corylifolia L. is used for a tonic and nursing one's energy. It can be also used for loss of virility. vitiligo. a skin disease, etc.. But a well known and often appreciated side effects f psoralens is the hyperpigmentation caused by this treatment. A women who used the herbal drug-mixed-medicine named'sobaeksu' to treat her vitiligo made a complaint against the orinetal medical doctor. She complained that her skin got burned to 2nd degree by the liquid. 'sobaeksu' through a medical celtficate. So we analyzed the components of that liquid with gas chromatography and gas chromatography/mass spectometry. It has 57.3% ethyl alcohol and two kinds of psoralens. Psoralens were psoralen and angelicin and each one of their contained quantity was 0.128mg/ml and 0.123mg/ml.