• Title/Summary/Keyword: Mouse skin melanoma cell

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New Whitening agent: Kojyl-APPA

  • Hwang, Jae-Sung;Kim, Duck-Hee;Soomi Anh;Baek, Heung-Soo;Park, Hyunjung -Jin;Lee, Jin-Young;Lee, Byeong-Gon;Ihseop Chang;Kang, Hak-Kee
    • 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.

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Cancer Prevention with Green Tea and Its Principal Constituent, EGCG: from Early Investigations to Current Focus on Human Cancer Stem Cells

  • Fujiki, Hirota;Watanabe, Tatsuro;Sueoka, Eisaburo;Rawangkan, Anchalee;Suganuma, Masami
    • Molecules and Cells
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    • v.41 no.2
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    • pp.73-82
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    • 2018
  • Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes groundbreaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young's moduli, i.e., cell stiffness, for human lung cancer cell lines and inhibition of cell motility and 5) Synergistic enhancement of anticancer activity against human cancer cell lines with the combination of EGCG and anticancer compounds. In the second part, we became interested in cancer stem cells (CSCs). 1) Cancer stem cells in mouse skin carcinogenesis by way of introduction, after which we discuss two subjects from our review on human CSCs reported by other investigators gathered from a search of PubMed, 2) Expression of stemness markers of human CSCs compared with their parental cells, and 3) EGCG decreases or increases the expression of mRNA and protein in human CSCs. On this point, EGCG inhibited self-renewal and expression of pluripotency-maintaining transcription factors in human CSCs. Human CSCs are thus a target for cancer prevention and treatment with EGCG and green tea catechins.

Effect of ethanol extract from mixture including Angelicae Dahuricae Radix on Dermal Anti-aging and Whitening (백지를 포함하는 한약재 복합 에탄올 추출물이 피부 항노화 및 미백에 미치는 영향)

  • Youn, Seok Na;Kim, Yoo Jin;Lee, Ye Ji;Kim, Mi Ryeo;Yoo, Wang Keun
    • The Korea Journal of Herbology
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    • v.34 no.6
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    • pp.109-115
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    • 2019
  • Objective : Herbal medicinal mixture (JMB) are consisted of Caryophylli Flos, Aucklandiae Radix, and Angelicae Dahuricae Radix. Each of these herbal medicines has studied on anti-aging effect in vitro. So this study was conducted to investigate efficacy and potency of JMB extract on dermal anti-aging and whitening. Methods : The JMB was extracted at room temperature by 80% ethanol. Collagenase and elastase inhibition activity in JMB ethanol extract were determined at 10, 50, 100, 500, 1000 mg/ml concentrations by colorimetric method. The toxic range of JMB ethanol extract was evaluated using MTT assay. Also, The inhibitory effect of JMB ethanol extract on tyrosinase activity and melanin contents in mouse melanoma cell line (B16F10 cell) was identified at 50, 100, 200 ㎍/㎖ levels by spectrometric assay. In each analysis, EGCG (epigallocatechin gallate) and Kojic acid were used as positive controls, respectively. Results : The elastase and collagenase inhibitory activity of JMB ethanol extract increased dose dependently. Also, The MTT assay showed that JMB, up to 400 ㎍/㎖ concentration, exhibited no toxic effect to the B16F10 cell. And following the JMB ethanol extract treat, cellular melanin contents and tyrosinase activity were dose-dependently decreased compared to those of control. Conclusion : These results suggest that JMB ethanol extract has effects to inhibitory activity on dermal wrinkle enzyme and melanogenesis. Therefore, JMB has applicable benefits for development of materials or products to have whitening and anti-aging functions on skin.

Skin Whitening Effects of Angelica koreana and Cnidium monnieri Extracts (강활과 벌사상자 추출물의 피부 미백효과)

  • Cho, Wan Goo;Kim, Cheong Tack
    • Journal of Digital Convergence
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    • v.12 no.4
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    • pp.419-425
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    • 2014
  • The objective of this study is to estimate the inhibition of skin melanin formation by extract of Angelica koreana and Cnidium monnieri and the possibility of functional cosmetic materials through anti-irritation and stability test. The extract used in this experiment is White-$AK^{TM}$ and the INCI name is Osthole. The main component of White-$AK^{TM}$ was identified as coumarin and EC50 value was 2.7ppm by mouse melanoma B 16 cell test. White-$AK^{TM}$ showed inhibitory effects 100 times lower concentration than arbutin. The main mechanism for skin whitening effect thought to be inhibition of tyrosinase-related gene expression. The basic essence formulation of White-$AK^{TM}$ 5% solution applied to the skin showed the effect of relieving skin irritation. White-$AK^{TM}$ in an opaque container, under UV conditions for 4 weeks, and showed close to 100% recovery and 97% recovery under $50^{\circ}C$ for 4 weeks. Therefore, it is thought that White-$AK^{TM}$ which helps skin whitening, relieving skin irritation and stable in UV condition is able to be used as the functional component in the cosmetic formulation.

The Melanin Inhibition, Anti-aging and Anti-inflammation Effects of Portulaca oleracea Extracts on Cells (쇠비름 추출물의 미백 및 항노화, 항염증 효과)

  • Zhang, Rui;Lee, Hyun-Jin;Yoon, Yeong-Min;Kim, Su-Mi;Kim, Hyun-Sook;Li, Shun Hua;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.4
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    • pp.397-402
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    • 2009
  • The Portulaca oleracea (P. oleracea) is a popular herbal medicine in East Asia that was known to possess detoxification, antifebrile and antifungal effects. In the present study, we examined the biological activities of ethanol extracts of P. oleracea under various conditions with NIH3T3, B16F10, and MCF-7 cell line model systems. Extracts of P. oleracea (0.5 mg/ml) showed inhibition of expression of tyrosinase, but does not suppress either of TYRP-1 or DCT expression on B16F10 cells. Extracts of P. oleracea (2 mg/ml) showed anti-inflammatory effects on TNF-$\alpha$-stimulated NIH3T3/$NF{\kappa}B$-Luc cells and increase of the synthesis of collagen on NIH3T3 (wild type) cells. These results suggest that extracts of P. oleracea could be used as a functional biomaterial in developing a skin whitening agent and having the anti-inflammatory, anti-wrinkle, and anti-aging activities.

Development of Natural Antioxidants and Whitening Agents for Cosmeceuticals

  • Kim, Jong-Pyung
    • 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.

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Effect of Aqueous Extract from Asiasari Radix on ${\alpha}$-melanocyte Stimulating Hormone Induced Melanogenesis in B16F10 Melanoma Cells (세신의 열수추출물이 ${\alpha}$-melanocyte Stimulating Hormone에 의해 유도된 B16F10 세포의 멜라닌 생성에 미치는 영향)

  • Lee, Jun-Hyuk;Shin, Dong-Yeok;Choi, Yung-Hyun;Chung, Kyung-Tae;Kang, Byoung-Won;Jeong, Seong-Yun;Choi, Byung-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.649-653
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    • 2008
  • The aqueous extract from Asiasari radix (AEAR) was used to investigate the effect of ${\alpha}$-melanocyte stimulating hormone induced melanogenesis in B16F10 mouse melnoma cells. The treatment with AEAR at the 1.0 and 2.0 mg/ml level significantly inhibited the biosynthesis of melanin without changes of cell growth and morphology compared with untreated control. The AEAR-treated cells at the 2.0 mg/ml level were more efficient than commercial arbutin at 0.1 mg/ml. The tyrosinase activity also significantly decreased in AEAR-treated cells at the 1.0 and 2.0 mg/ml level. The Western analyses confirmed the slightly decreased expression of tyrosinase by AEAR treatment. These results indicate that AEAR may contribute to the inhibition of melanin biosynthesis through regulating tyrosinase activity and expression and serve as a new candidate in the design of new skin-whitening or therapeutic agents.

Melanogenesis regulatory constituents from Premna serratifolia wood collected in Myanmar

  • WOO, SO-YEUN
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.21-22
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    • 2019
  • Melanin is a mixture of pigmented biopolymers synthesized by epidermal melanocytes that determine the skin, eye, and hair colors. Melanocytes produce two different kinds of melanin, eumelanin (dark brown/black insoluble pigments found in dark skin and dark hair and pheomelanin (lighter red/yellow). The biological role of melanin is to prevent skin damage by ultraviolet (UV) radiation. However, the overproduction or deficiency of melanin synthesis could lead to serious dermatological problems, which include melasma, melanoderma, lentigo, and vitiligo. Therefore, regulating melanin production is important to prevent the pigmentation disorders. Myanmar has a rich in natural resources. However, the chemical constituents of these natural resources in Myanmar have not been fully investigated. In the effort to search for compounds with anti-melanin deposition activity from Myanmar natural resources, five plants were collected in Myanmar. Extracts of these collected five plants were tested for anti-melanin deposition activity against a mouse melanoma cell line (B16-F10) induced with ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH) and 3-isobutyl-1-methylxanthine (IBMX), and their anti-melanin deposition activities were compared with the positive control, arbutin. Among the tested extracts, the CHCl3 extracts of the Premna serratifolia (syn: P. integrifolia) wood showed anti-melanin deposition activities with IC50 values of $81.3{\mu}g/mL$. Hence, this study aims to identify secondary metabolites with anti-melanin deposition activity from P. serratifolia wood of Myanmar. P. serratifolia belongs to the Verbenaceae family and is widely distributed in near western sea coast from South Asia to South East Asia, which include India, Malaysia, Vietnam, Cambodia, and Sri Lanka. People in Tanintharyi region located in the southern part of Myanmar utilize the P. serratifolia, Sperethusa crenulata, Naringi crenulata, and Limonia acidissima as Thanaka, traditional cosmetics in Myanmar. Thanaka is applied in the form of paste onto skins to make it smooth and clear, as well as to prevent wrinkles, skin aging, excessive facial oil, pimples, blackheads, and whiteheads. However, the chemical constituents responsible for their cosmetic properties are yet to be identified. Moreover, the chemical constituents of P. serratifolia was almost uncharacterized. Investigation of the P. serratifolia chemical constituents is thus an attractive endeavor to discover new anti-melanin deposition active compounds. The investigation of the chemical constituents of the active CHCl3 extract of P. serratifolia led to isolation of four new lignoids, premnan A (1), premnan B (2), taungtangyiol C (3), and 7,9-dihydroxydolichanthin B (4), together with premnan C (5) (assumed to be an artifact), one natural newlignoid,(3R,4S)-4-(1,3-benzodioxol-5-ylcarbonyl)-3-[(R)-1-(1,3-benzo dioxol-5-yl)-1-hydroxy methyl]tetrahydro-2-furanone (6), and five known compounds (7-11)1,2). The structures of all isolated compounds were determined on the basis of their spectroscopic data and by comparison with the reported literatures. The absolute configurations of 1-3 and 5 were also determined by optical rotation and circular dichroism (CD) data analyses1). The anti-melanin deposition activities of all the isolated compounds were evaluated against B16-F10 cell line. 7,9-Dihydroxydolichanthin B (4) and ($2{\alpha},3{\alpha}$)-olean-12-en-28-oic acid (11) showed strong anti-melanin deposition activities with IC50 values of 18.4 and $11.2{\mu}M$, respectively, without cytotoxicity2). On the other hand, compounds 1-3, 5, and 7 showed melanogenesis enhancing activities1). To better understand their anti-melanin deposition mechanism, the effects of 4 and 11 on tyrosinase activities were investigated. The assay indicated that compounds 4 and 11 did not inhibit tyrosinase. Furthermore, we also examined the mRNA expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Compounds 4 and 11 down-regulated the expression of Tyr and Mitf mRNAs, respectively. Although the P. serratifolia wood has been used as traditional cosmetics in Myanmar for centuries, there are no scientific evidences to support its effectiveness as cosmetics. Investigation of the anti-melanin deposition activity of the chemical constituents of P. serratifolia thus provided insight into the effectiveness of the P. serratifolia wood as a cosmetic agent.

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Physiological Activity and Physicochemical Properties of Condensed Prunus mume Juice Prepared with Pectinase (Pectinase처리를 한 매실 농축액의 이화학적 특성 및 생리활성)

  • Kim, Jeong-Ho;Cho, Hyun-Dong;Won, Yeong-Seon;Park, Wool-Lim;Lee, Kwan-Woo;Kim, Hyuk-Joo;Seo, Kwon-Il
    • Journal of Life Science
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    • v.28 no.11
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    • pp.1369-1378
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    • 2018
  • Prunus mume Siebold & Zucc., a member of the Rosaceae family (called Maesil in Korea), has been widely distributed in East Asia, e.g. Korea, Japan and China, and its fruit has been used as a traditional drug and health food. In this study, we evaluated physicochemical properties and physiological activities of condensed Prunus mume juice treated with pectinase (PJ). The values of total acidity, pH, sugar contents, turbidity moisture content of the PJ were 35.81%, 2.73, $54.36^{\circ}Brix$, 2.75 and 51.32%, respectively. The PJ had effective DPPH radical scavenging activity, reducing power effect, $H_2O_2$ scavenging activity and ${\beta}$-carotene bleaching effect. DPPH radical scavenging activities of PJ was 46.31%; their reducing power ($OD_{700}$) was 1.80; $H_2O_2$ scavenging activity of PJ was 91.62%; and ${\beta}$-carotene bleaching effect of PJ was 73.02%. Also, PJ showed effective levels of ${\alpha}$-glucosidase inhibition activity. The cell viability was measured by SRB assay. The PJ significantly decreased the cell viability of mouse melanoma cells (B16) and human melanoma cells (SK-MEL-2 and SK-MEL-28) in a dose-dependent manner, however, there was no effect on human keratinocyte HaCaT. In morphological study, PJ-treated SK-MEL-2 cells showed distorted and shrunken cell masses. Total polyphenol contents and total flavonoid contents of PJ were 588.31 mg% (gallic acid equivalent) and 860.45 mg% (rutin equivalent). The antiproliferative effect of PJ seems to be associated with the antioxidant activity of its flavonoid and polyphenol contents. In conclusion, PJ may be beneficial in development of a functional food material.