• 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.

• The Korean Journal of Food And Nutrition
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• v.15 no.2
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• pp.137-143
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• 2002

Lyophilizate of immatured wax gourd extract was 3.1 %, matured wax gourd extract was 1.0%, and its main ingredient was sugar, which accounts for 89.7% in total residue. In matured wax gourd, pectin contents was 4.11 mg/ml, and in immatured wax gourd 4.43 mg/m1. In matured wax gourd sarcocarp, sugar contents was 0.1% of sucrose, 0.32% of glucose, 0.35% of fructose, the first unidentified sugar was 0.06% and the second was 0.04%, and all total 0.87%. In sarcocarp of immatured wax gourd, sucrose was 0.33%, glucose was 1.04%, frutcose was 1.12%, and the first unidentified sugar 0.18%, and the second was 0.l2, which total 2.79%. In matured wax gourd core, pH was 4.64, sarcocarp 4.94, immatured wax gourd core 4,96, sarcocarp 5.40. According to the organic acid analysis, in sarcocarp of matured wax gourd, citric acid of 0.409 was contained, magic acid 0.084, succnic acid 0.048%, in matured wax gourd core, citric acid was 0.648, magic acid 0.127, succinc acid 0.058%, in immatured wax gourd, citric acid 0.023, magic acid 0.219, succinic acid 0.298%, in immutured wax gourd, citric acid was 0.039, malic acid 0.350, succinic 0.224%. Fumaric acid was trace in all cases. Total organic acid in matured wax gourd core was 0.833, immatured wax gourd core was 0.624 and immatured wax gourd sarcocarp was 0.546, matured wax gourd sarcocarp was 0,541%. In inhibition rate to propionibacterium acnes, control was 0(ø, cm), wax gourd that was not heated was 2.6, and wax gourd which was heated was 2.5, concentrated by 1/5 was 1.9, wax gourd by 1/10 was 2.5, freezing dry was 2.3. Wax gourd which not heated on producing melanin in B-16 melanoma cell, the melanins forming unit was 15$\mu$1/m1 in addition of 0.01%, while that as a control was 29$\mu$1/m1.