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BMC Complementary Medicine and Therapies

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Open Access 01-12-2017 | Research article

N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms

Authors: Yueh-Hsiung Kuo, Chien-Chia Chen, Po-Yuan Wu, Chin-Sheng Wu, Ping-Jyun Sung, Chien-Yih Lin, Hsiu-Mei Chiang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

The derivative of caffeamide exhibits antioxidant and antityrosinase activity. The activity and mechanism of N-(4-methoxyphenyl) caffeamide (K36E) on melanogenesis was investigated.

Methods

B16F0 cells were treated with various concentrations of K36E; the melanin contents and related signal transduction were studied. Western blotting assay was applied to determine the protein expression, and spectrophotometry was performed to identify the tyrosinase activity and melanin content.

Results

Our results indicated that K36E reduced α-melanocyte-stimulating hormone (α-MSH)-induced melanin content and tyrosinase activity in B16F0 cells. In addition, K36E inhibited the expression of phospho-cyclic adenosine monophosphate (cAMP)-response element-binding protein, microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1). K36E activated the phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK3β), leading to the inhibition of MITF transcription activity. K36E attenuated α-MSH induced cAMP pathways, contributing to hypopigmentation.

Conclusions

K36E regulated melanin synthesis through reducing the expression of downstream proteins including p-CREB, p-AKT, p-GSK3β, tyrosinase, and TRP-1, and activated the transcription factor, MITF. K36E may have the potential to be developed as a skin whitening agent.

Solano F, Briganti S, Picardo M, Ghanem G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 2006;19(6):550–71.CrossRefPubMed

Chiang HM, Chen HW, Huang YH, Chan SY, Chen CC, Wu WC, Wen KC. Melanogenesis and natural hypopigmentation agents. 2012.

Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007;21(4):976–94.CrossRefPubMed

Kondo T, Hearing VJ. Update on the regulation of mammalian melanocyte function and skin pigmentation. Expert Rev Dermatol. 2011;6(1):97–108.CrossRefPubMedPubMedCentral

Yamaguchi Y, Hearing VJ. Physiological factors that regulate skin pigmentation. Biofactors. 2009;35(2):193–9.CrossRefPubMedPubMedCentral

Hearing VJ. Milestones in melanocytes/melanogenesis. J Invest Dermatol. 2011;131(E1):E1.CrossRefPubMed

Chiang HM, Chien YC, Wu CH, Kuo YH, Wu WC, Pan YY, Su YH, Wen KC. Hydroalcoholic extract of Rhodiola rosea L. (Crassulaceae) and its hydrolysate inhibit melanogenesis in B16F0 cells by regulating the CREB/MITF/tyrosinase pathway. Food Chem Toxicol. 2014;65:129–39.CrossRefPubMed

Wen KC, Chang CS, Chien YC, Wang HW, Wu WC, Wu CS, Chiang HM. Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced melanogenesis. Int J Mol Sci. 2013;14(12):23420–40.CrossRefPubMedPubMedCentral

Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL, Igras VE, D’Orazio J, Fung CY, Schanbacher CF, Granter SR, et al. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell. 2007;128(5):853–64.CrossRefPubMed

10.

Hocker TL, Singh MK, Tsao H. Melanoma genetics and therapeutic approaches in the 21st century: moving from the benchside to the bedside. J Invest Dermatol. 2008;128(11):2575–95.CrossRefPubMed

11.

Drira R, Sakamoto K. Isosakuranetin, a 4′-O-methylated flavonoid, stimulates melanogenesis in B16BL6 murine melanoma cells. Life Sci. 2015;143:43–9.CrossRefPubMed

12.

Chou TH, Ding HY, Lin RJ, Liang JY, Liang CH. Inhibition of melanogenesis and oxidation by protocatechuic acid from Origanum vulgare (oregano). J Nat Prod. 2010;73(11):1767–74.CrossRefPubMed

13.

Yeom GG, Min S, Kim SY. 2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and inflammation in a UVA-induced melanoma/keratinocytes co-culture system. Int Immunopharmacol. 2014;18(2):262–9.CrossRefPubMed

14.

Chiang HM, Chen CW, Lin TY, Kuo YH. N-phenethyl caffeamide and photodamage: Protecting skin by inhibiting type I procollagen degradation and stimulating collagen synthesis. Food Chem Toxicol. 2014;72C:154–61.CrossRef

15.

Kuo YH, Chen CW, Chu Y, Lin P, Chiang HM. In Vitro and In Vivo Studies on Protective Action of N-Phenethyl Caffeamide against Photodamage of Skin. PLoS One. 2015;10(9):e0136777.CrossRefPubMedPubMedCentral

16.

Shimoda H, Shan SJ, Tanaka J, Maoka T. beta-Cryptoxanthin suppresses UVB-induced melanogenesis in mouse: involvement of the inhibition of prostaglandin E2 and melanocyte-stimulating hormone pathways. J Pharm Pharmacol. 2012;64(8):1165–76.CrossRefPubMed

17.

Okombi S, Rival D, Bonnet S, Mariotte AM, Perrier E, Boumendjel A. Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte-tyrosinase. Bioorg Med Chem Lett. 2006;16(8):2252–5.CrossRefPubMed

18.

Bellei B, Pitisci A, Izzo E, Picardo M. Inhibition of melanogenesis by the pyridinyl imidazole class of compounds: possible involvement of the Wnt/beta-catenin signaling pathway. PLoS One. 2012;7(3):e33021.CrossRefPubMedPubMedCentral

19.

Wang L, Lu AP, Yu ZL, Wong RN, Bian ZX, Kwok HH, Yue PY, Zhou LM, Chen H, Xu M, et al. The melanogenesis-inhibitory effect and the percutaneous formulation of ginsenoside Rb1. AAPS PharmSciTech. 2014;15(5):1252–62.CrossRefPubMedPubMedCentral

20.

Suwannalert P, Kariya R, Suzu I, Okada S. The effects of Salacia reticulata on anti-cellular oxidants and melanogenesis inhibition in alpha-MSH-stimulated and UV irradiated B16 melanoma cells. Nat Prod Commun. 2014;9(4):551–4.PubMed

21.

Chou YC, Sheu JR, Chung CL, Chen CY, Lin FL, Hsu MJ, Kuo YH, Hsiao G. Nuclear-targeted inhibition of NF-kappaB on MMP-9 production by N-2-(4-bromophenyl) ethyl caffeamide in human monocytic cells. Chem Biol Interact. 2010;184(3):403–12.CrossRefPubMed

22.

Chiang HM, Lin JW, Hsiao PL, Tsai SY, Wen KC. Hydrolysates of citrus plants stimulate melanogenesis protecting against UV-induced dermal damage. Phytother Res. 2011;25(4):569–76.CrossRefPubMed

23.

Chiang H-M, Ko Y, Shih I, Wen K. Development of Wine Cake as a Skin-Whitening Agent and Humectant. J Food Drug Anal. 2011;19(2):223–9.

24.

Chiang HM, Chen HC, Lin TJ, Shih IC, Wen KC. Michelia alba extract attenuates UVB-induced expression of matrix metalloproteinases via MAP kinase pathway in human dermal fibroblasts. Food Chem Toxicol. 2012;50(12):4260–9.CrossRefPubMed

25.

Salucci S, Burattini S, Battistelli M, Buontempo F, Canonico B, Martelli AM, Papa S, Falcieri E. Tyrosol prevents apoptosis in irradiated keratinocytes. J Dermatol Sci. 2015;80(1):61–8.CrossRefPubMed

26.

Zhang Y, Helke KL, Coelho SG, Valencia JC, Hearing VJ, Sun S, Liu B, Li Z. Essential role of the molecular chaperone gp96 in regulating melanogenesis. Pigment Cell Melanoma Res. 2014;27(1):82–9.CrossRefPubMed

27.

Park H, Song KH, Jung PM, Kim JE, Ro H, Kim MY, Ma JY. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression. Evid Based Complement Alternat Med : eCAM. 2013;2013:965312.PubMedPubMedCentral

28.

Chiang HM, Lin TJ, Chiu CY, Chang CW, Hsu KC, Fan PC, Wen KC. Coffea arabica extract and its constituents prevent photoaging by suppressing MMPs expression and MAP kinase pathway. Food Chem Toxicol. 2011;49(1):309–18.CrossRefPubMed

29.

Chiang H-M, Chiu H-H, Liao S-T, Chen Y-T, Chang H-C, Wen K-C. Isoflavonoid-Rich Flemingia macrophylla Extract Attenuates UVB-Induced Skin Damage by Scavenging Reactive Oxygen Species and Inhibiting MAP Kinase and MMP Expression. Evid Based Complement Alternat Med. 2013;2013:12.

30.

Bertolotto C, Bille K, Ortonne JP, Ballotti R. Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product. J Cell Biol. 1996;134(3):747–55.CrossRefPubMed

31.

Korner A, Pawelek J. Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science (New York, NY). 1982;217(4565):1163–5.CrossRef

32.

Tripathi RK, Hearing VJ, Urabe K, Aroca P, Spritz RA. Mutational mapping of the catalytic activities of human tyrosinase. J Biol Chem. 1992;267(33):23707–12.PubMed

33.

Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004;84(4):1155–228.CrossRefPubMed

34.

Fu YT, Lee CW, Ko HH, Yen FL. Extracts of Artocarpus communis decrease alpha-melanocyte stimulating hormone-induced melanogenesis through activation of ERK and JNK signaling pathways. ScientificWorldJournal. 2014;2014:724314.PubMedPubMedCentral

35.

Chou TH, Ding HY, Hung WJ, Liang CH. Antioxidative characteristics and inhibition of alpha-melanocyte-stimulating hormone-stimulated melanogenesis of vanillin and vanillic acid from Origanum vulgare. Exp Dermatol. 2010;19(8):742–50.CrossRefPubMed

36.

Kumar KJ, Yang JC, Chu FH, Chang ST, Wang SY. Lucidone, a novel melanin inhibitor from the fruit of Lindera erythrocarpa Makino. Phytother Res. 2010;24(8):1158–65.PubMed

37.

Liu Q, Kim C, Jo YH, Kim SB, Hwang BY, Lee MK. Synthesis and Biological Evaluation of Resveratrol Derivatives as Melanogenesis Inhibitors. Molecules (Basel, Switzerland). 2015;20(9):16933–45.CrossRef

38.

Jimenez-Cervantes C, Solano F, Kobayashi T, Urabe K, Hearing VJ, Lozano JA, Garcia-Borron JC. A new enzymatic function in the melanogenic pathway. The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TRP1). J Biol Chem. 1994;269(27):17993–8000.PubMed

39.

Kobayashi T, Urabe K, Winder A, Jimenez-Cervantes C, Imokawa G, Brewington T, Solano F, Garcia-Borron JC, Hearing VJ. Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J. 1994;13(24):5818–25.PubMedPubMedCentral

40.

Gaggioli C, Busca R, Abbe P, Ortonne JP, Ballotti R. Microphthalmia-associated transcription factor (MITF) is required but is not sufficient to induce the expression of melanogenic genes. Pigment Cell Res. 2003;16(4):374–82.CrossRefPubMed

41.

Khaled M, Larribere L, Bille K, Aberdam E, Ortonne JP, Ballotti R, Bertolotto C. Glycogen synthase kinase 3beta is activated by cAMP and plays an active role in the regulation of melanogenesis. J Biol Chem. 2002;277(37):33690–7.CrossRefPubMed

42.

Khaled M, Larribere L, Bille K, Ortonne JP, Ballotti R, Bertolotto C. Microphthalmia associated transcription factor is a target of the phosphatidylinositol-3-kinase pathway. J Invest Dermatol. 2003;121(4):831–6.CrossRefPubMed

43.

Shao YY, Chen CC, Wang HY, Chiu HL, Hseu TH, Kuo YH. Chemical constituents of Antrodia camphorata submerged whole broth. Nat Prod Res. 2008;22(13):1151–7.CrossRefPubMed

44.

Oka M, Nagai H, Ando H, Fukunaga M, Matsumura M, Araki K, Ogawa W, Miki T, Sakaue M, Tsukamoto K, et al. Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells. J Invest Dermatol. 2000;115(4):699–703.CrossRefPubMed

45.

Busca R, Ballotti R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 2000;13(2):60–9.CrossRefPubMed

46.

Shibahara S, Takeda K, Yasumoto K, Udono T, Watanabe K, Saito H, Takahashi K. Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation. J Invest Dermatol Symp Proc/Soc Invest Dermatol, Inc [and] Eur Soc Dermatol Res. 2001;6(1):99–104.CrossRef

47.

Lee JY, Choi HJ, Chung TW, Kim CH, Jeong HS, Ha KT. Caffeic Acid Phenethyl Ester Inhibits Alpha-Melanocyte Stimulating Hormone-Induced Melanin Synthesis through Suppressing Transactivation Activity of Microphthalmia-Associated Transcription Factor. J Nat Prod. 2013;76(8):1399–405.CrossRefPubMed

48.

Huang GJ, Huang SS, Lin SS, Shao YY, Chen CC, Hou WC, Kuo YH. Analgesic effects and the mechanisms of anti-inflammation of ergostatrien-3beta-ol from Antrodia camphorata submerged whole broth in mice. J Agric Food Chem. 2010;58(12):7445–52.CrossRefPubMed

49.

Tsai TC, Tung YT, Kuo YH, Liao JW, Tsai HC, Chong KY, Chen HL, Chen CM. Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. J Ethnopharmacol. 2015;159:113–21.CrossRefPubMed

Title: N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms
Authors: Yueh-Hsiung Kuo
Chien-Chia Chen
Po-Yuan Wu
Chin-Sheng Wu
Ping-Jyun Sung
Chien-Yih Lin
Hsiu-Mei Chiang
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-016-1554-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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