• 제목/요약/키워드: tyrosinase-related protein-1

검색결과 175건 처리시간 0.029초

Melanin 합성을 촉진하는 흑임자 에탄올추출물의 효능 (Black Sesame Ethanolic Extract Promotes Melanin Synthesis)

  • 전소정;김문무
    • 생명과학회지
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    • 제27권12호
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    • pp.1452-1461
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    • 2017
  • 백발화과정은 인간의 노화의 표현형 중 하나로 노화의 지표이다. 시간이 지남에 따라 사람 모낭에 melanocyte의 melanin 생성이 줄어들게 된다. 이의 원인으로는 모낭내 tyrosinase 활성의 감소와 활성 산소 종 중 $H_2O_2$에 의한 축적을 통해 나타난다. 천연물중에서 예로부터 흑모를 유도한다는 흑임자주정추출물의 비극성 층과 극성 층을 분리하여 항산화 효과 및 B16F1에서 melanin 생성 촉진 효과를 조사하였다. 항산화 실험에서 SBEEP와 SBEEO는 DPPH 소거 효과를 보여주지 않았고, 낮은 환원력을 보여주었다. SBEEP는 $8{\mu}g/ml$ 이상에서 세포 독성이 나타났고 SBEEO는 $4{\mu}g/ml$ 이상에서 세포 독성 효과를 보여주었다. SBEEP와 SBEEO는 in vitro에서 tyrosinase 활성과 DOPA 산화 활성에 대한 높은 melanin 합성 효과를 보여주었고, 살아있는 세포에서는 SBEEP처리군은 SBEEO 처리군보다 높은 melanin 합성 촉진 효과가 나타났다. 세포 내 melanin 생성에 효과가 있는 SBEEP는 melanin 합성 기전에서 중요한 효소인 TRP-2의 발현을 통해 melanin 생성을 촉진한다는 것을 발견하였다. 이러한 결과들은 흑임자의 SBEEP가 melanin 합성을 촉진할 수 있다는 가능성을 시사하고 있다.

Acremonidin E produced by Penicillium sp. SNF123, a fungal endophyte of Panax ginseng, has antimelanogenic activities

  • Kim, Kyuri;Jeong, Hae-In;Yang, Inho;Nam, Sang-Jip;Lim, Kyung-Min
    • Journal of Ginseng Research
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    • 제45권1호
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    • pp.98-107
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    • 2021
  • Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

광곽향 추출물의 멜라닌 생성 저해 효과 (The Inhibitory Effects of Pogostemon cablin Bentham Extract on Melanogenesis)

  • 배성윤;이응지;손락호;이용화
    • 대한화장품학회지
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    • 제35권1호
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    • pp.33-39
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    • 2009
  • 본 연구는 천연 미백소재 개발을 위하여 광곽향 추출물과 광곽향 추출물에서 분리한 활성물질의 멜라닌 생성에 연관된 생리활성을 분석하였다. 광곽향 추출물은 $100{\mu}g/mL$ 이하에서 세포 독성이 없는 것으로 확인되었으며 free radical 소거능(DPPH)과 superoxide radical 소거능 결과는 각각 $IC_{50}=24.2{\pm}2.85{\mu}g/mL$, $IC_{50}=118{\pm}0.43{\mu}g/mL$을 나타내었다. B16 melanoma 세포에서의 멜라닌 생합성 저해 효과는 $20{\mu}g/mL$ 농도의 광곽향 추출물을 72 h 동안 처리한 세포에서 멜라닌 억제율이 23 %로 나타났으며, $50{\mu}g/mL$ 농도에서 세포 내 tyrosinase의 활성을 18 % 저해하였다. 이러한 광곽향 추출물의 활성물질을 분리하여 $^{1}H$-NMR, $^{13}C$-NMR, Mass analysis 등의 기기분석을 실시한 결과 sesquiterpene 계열의 활성물질인 patchouli alcohol으로 동정되었고, patchouli alcohol의 free radical 소거능과 superoxide radical 소거능 결과는 각각 $IC_{50}=3.14{\pm}0.12{\mu}g/mL$, $IC_{50}=49{\pm}3.24{\mu}g/mL$을 나타내었다. 또한 멜라닌 저해효과를 확인한 결과 $IC_{50}=3.9{\mu}g/mL$으로 나타났으며, $10{\mu}g/mL$ 농도에서 세포 내 tyrosinase의 활성을 40 % 저해하였다. Western blot을 이용하여 tyrosinase와 tyrosinase related protein-2 (TRP-2) 단백질의 발현 감소를 확인하였다. 그러므로 광곽향 추출물과 patchouli alcohol은 우수한 미백 효능을 갖는 화장품 소재로서 개발 가능성이 클 것으로 기대된다.

Sageretia thea fruit extracts rich in methyl linoleate and methyl linolenate downregulate melanogenesis via the Akt/GSK3β signaling pathway

  • Ko, Gyeong-A;Shrestha, Sabina;Cho, Somi Kim
    • Nutrition Research and Practice
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    • 제12권1호
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    • pp.3-12
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    • 2018
  • BACKGROUND/OBJECTIVES: Sageretia thea is traditionally used as a medicinal herb to treat various diseases, including skin disorders, in China and Korea. This study evaluated the inhibitory effect of Sageretia thea fruit on melanogenesis and its underlying mechanisms in B16F10 mouse melanoma cells. The active chemical compounds in anti-melanogenesis were determined in Sageretia thea. MATERIALS/METHODS: Solvent fractions from the crude extract were investigated for anti-melanogenic activities. These activities and the mechanism of anti-melanogenesis in B16F10 cells were examined by determining melanin content and tyrosinase activity, and by performing western blotting. RESULTS: The n-hexane fraction of Sageretia thea fruit (HFSF) exhibited significant anti-melanogenic activity among the various solvent fractions without reducing viability of B16F10 cells. The HFSF suppressed the expression of tyrosinase and tyrosinase-related protein 1 (TRP1). The reduction of microphthalmia-associated transcription factor (MITF) expression by the HFSF was mediated by the Akt/glycogen synthase kinase 3 beta ($GSK3{\beta}$) signaling pathway, which promotes the reduction of ${\beta}-catenin$. Treatment with the $GSK3{\beta}$ inhibitor 6-bromoindirubin-3'-oxime (BIO) restored HFSF-induced inhibition of MITF expression. The HFSF bioactive constituents responsible for anti-melanogenic activity were identified by bioassay-guided fractionation and gas chromatography-mass spectrometry analysis as methyl linoleate and methyl linolenate. CONCLUSIONS: These results indicate that HFSF and its constituents, methyl linoleate and methyl linolenate, could be used as whitening agents in cosmetics and have potential for treating hyperpigmentation disorders in the clinic.

마우스 흑색종 B16F10세포에서 loganin의 티로시나아제 발현 억제를 통한 멜라닌 생성 억제에 대한 기전연구 (Loganin Inhibits α-MSH and IBMX-induced Melanogenesis by Suppressing the Expression of Tyrosinase in B16F10 Melanoma Cells)

  • 정희진;방은진;김병무;정성호;이길한;정해영
    • 생명과학회지
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    • 제29권11호
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    • pp.1200-1207
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    • 2019
  • Loganin은 Corni fructus의 주요 iridoid glycoside이며 항염증, 항당뇨 그리고 뇌신경보호 효과 등이 보고되었다. 본 연구에서는 ${\alpha}-MSH$와 IBMX처리된 B16F10세포에서 loganin의 melanogenesis억제효과의 신호전달 경로를 조사하였다. Loganin의 미백 활성을 확인하기 위해 B16F10세포에서 $1{\mu}m$에서 $20{\mu}m$사이의 농도를 처리하여 세포독성 실험을 수행한 결과 최대 $20{\mu}m$농도에서 독성을 나타내지 않았다. 또한 loganin은 ${\alpha}-MSH$와 IBMX처리된 B16F10세포에서 농도-의존적으로 멜라닌 생성을 감소시키는 것을 확인하였다. 또한 loganin의 멜라닌 생성을 억제하는 신호전달 경로를 Western blotting을 실시하여 조사하였다. Western blot결과에 따르면 loganin은 ${\alpha}-MSH$와 IBMX 처리된 B16F10세포에서 증가된 CREB인산화(Ser133)와 MITF 발현 및 tyrosinase의 유전자 발현을 감소시켰고 ERK의 인산화를 증가시켜 melanin 생성을 억제하였다. 결론적으로 loganin은 ${\alpha}-MSH$와 IBMX에 의해 유도된 과도한 멜라닌 합성을 CREB인산화와 MITF 및 tyrosinase의 유전자 발현을 억제하고 ERK의 활성화를 통해 멜라닌 합성을 감소됨을 확인하였다. 따라서 loganin은 과색소 침착과 관련된 피부질환의 보호제로서 활용될 가능성을 가지는 것으로 사료된다.

Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways

  • Jianzeng Liu ;Xiaohao Xu ;Jingyuan Zhou;Guang Sun ;Zhenzhuo Li;Lu Zhai ;Jing Wang ;Rui Ma ;Daqing Zhao;Rui Jiang ;Liwei Sun
    • Journal of Ginseng Research
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    • 제47권6호
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    • pp.714-725
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    • 2023
  • Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

Melanin Synthesis Inhibitory Effect of Eriobotryae Folium Extracts & Eriobotryae Folium and Phreatic Water Mixture

  • Choi, Jae-Song;Park, Jung-Hwan;Koh, Young-Mee;Kwak, Jin-young;Ahn, Taek-Won
    • 대한한의학회지
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    • 제38권4호
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    • pp.62-81
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    • 2017
  • Objectives: As interests in the beauty of skin is growing continuously, more people are focusing on white and clean skin. Melanin is the major factor that determines skin color. The abnormal concentration of melanin causes various skin diseases such as vitiligo, freckles, and melasma. This study investigated the inhibitory effect of Eriobotryae Folium extracts (EF) with phreatic water (PW) on the melanin synthesis. Methods: The effect of EF on melanin synthesis was evaluated by using mouse melanoma cells (B16F10). To define the mechanisms, real-time PCR and western blot were used. We also evaluated the inhibitory effects of EF and PW on melanin synthesis by using HRM-2 melanin-possessing hairless mice. After UVB irradiation, melanin differences between the skin parts that were treated and untreated with EF and PW. Levels of mRNA were measured by real-time quantitative PCR and histological analysis of the dorsal skin was conducted by hematoxylin and eosin staining. Results: EF inhibited various mechanisms of melanogenesis, and the effect was increased when combined with PW. In vitro experiments have shown that EF inhibited the expressions of tyrosinase related protein-1 (TRP-1) mRNA, tyrosinase mRNA, microphthalmia-associated transcription factor (MITF) mRNA and the tyrosinase inhibitory activation, but it stimulated the extracellular regulated kinase (ERK) mRNA expression. In vivo experiments have shown that EF prevented melanogenesis in the mice dorsal skin and inhibited TRP-1 mRNA expression. Also these effects were increased when combined with PW. Conclusions: EF and PW might be a new and effective treatment for whitening and treating pigmentation of skin.

측백엽(側柏葉)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향 (Effects of Thujae Orientalis Folium (TOF) on Gene Expression of Human melanoma cells (SK-MEL-2))

  • 정민영;김종한;박수연;최정화
    • 한방안이비인후피부과학회지
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    • 제23권2호
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    • pp.81-108
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    • 2010
  • Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

B16/F10 흑색종 세포에서 S-Adenosylhomocysteine Hydrolase 의 선택적 저해제 3-Deazaneplanocin A 에 의한 (Melanogenesis Promotion by 3-Deazaneplanocin A, a Specific Inhibitor of S-Adenosylhomocysteine Hydrolase, in B16/F10 Melanoma Cells)

  • 황윤정;부용출
    • 대한화장품학회지
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    • 제47권2호
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    • pp.107-121
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    • 2021
  • 백색증이나 백반증에서 관찰되는 피부 저색소침착은 유전적 요인, 후성유전적 요인 및 기타 요인에 의해 멜라닌 합성이 감소할 때 발생한다. 세포에서 멜라닌 합성을 촉진 할 수 있는 약물 후보를 확인하기 위해 141개의 세포 투과성 저분자 약물로 구성된 후성유전적 조절제 라이브러리를 스크리닝했다. B16/F10 쥐 흑색종 세포를 0.1 𝜇M에서 각 약물로 처리하고 멜라닌 합성 및 세포 생존력을 모니터링했다. 그 결과, (-)-네플라노신 A, 3-디아자네플라노신 A (DZNep) 및 DZNep 염산염이 세포 독성을 일으키지 않고 멜라닌 합성을 증가시키는 것으로 나타났다. 이 세 가지 구조적으로 관련된 약물은 세포 멜라닌 합성 및 세포 생존력에 유사한 용량 의존적 효과를 나타내었기 때문에 DZNep을 추가 실험을 위한 대표 약물로 선택하였다. DZNep는 세포내 멜라닌 함량과 티로시나제(TYR) 활성을 증가 시켰다. DZNep은 또한 mRNA와 단백질 수준에서 TYR, 티로시나제 관련 단백질 1 (TYRP1) 및 도파크롬 토토머라제 (DCT)의 발현을 유도했다. DZNep는 또한 멜라닌 합성의 주요 조절자인 소안구증 관련 전사 인자(MITF)의 mRNA와 단백질 발현을 유도했다. DZNep은 S-아데노실 호모시스테인 가수분해효소의 선택적 억제제이며 히스톤 메틸화효소를 저해하는 S-아데노실 호모시스테인의 세포내 축적을 유발하였다. 이 연구는 특정 세포 상황에서 S-아데노실 호모시스테인 가수분해효소를 표적함으로써 멜라닌 생성이 조절될 수 있음을 시사한다.

Melanogenesis regulatory constituents from Premna serratifolia wood collected in Myanmar

  • WOO, SO-YEUN
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2019년도 춘계학술대회
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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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