Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
권호 표지
DOI QR코드

DOI QR Code

Antimelanogenic and antioxidant effects of trimethoxybenzene derivatives: methyl 3,4,5-trimethoxybenzoate, ethyl 3,4,5-trimethoxybenzoate, methyl 3,4,5-trimethoxycinnamate, and ethyl 3,4,5-trimethoxycinnamate

  • Jaewon, Shin (Division of Applied Chemistry and Cosmetic Science, Dongduk Women's University) ;
  • Harim, Lee (Division of Applied Chemistry and Cosmetic Science, Dongduk Women's University) ;
  • Seunghyun, Ahn (Department of Applied Chemistry, Dongduk Women's University) ;
  • Won Seok, Jeong (RNS Inc. R&D Center) ;
  • CheongTaek, Kim (RNS Inc. R&D Center) ;
  • Seyeon, Park (Division of Applied Chemistry and Cosmetic Science, Dongduk Women's University)
  • Received : 2022.09.23
  • Accepted : 2022.10.26
  • Published : 2022.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

In this study, derivatives of trimethoxybenzene were investigated as inhibitors of melanogenesis. We examined the effects of methyl 3,4,5-trimethoxybenzoate (MTB), ethyl 3,4,5-trimethoxybenzoate (ETB), methyl 3,4,5-trimethoxycinnamate (MTC), and ethyl 3,4,5-trimethoxycinnamate (ETC). First, the inhibitory effects of these agents on melanin production were evaluated using α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. We found that all derivatives decreased α-MSH-induced melanin production in B16F10 melanoma cells; ETC showed a strong inhibitory effect at half of the concentration of the other derivatives. As tyrosinase is considered a key enzyme of melanogenesis, we also examined whether the derivatives inhibited tyrosinase activity. MTC and ETC reduced mushroom tyrosinase activity and expression levels of α-MSH-induced B16F10 cellular tyrosinase protein. Inhibitory effects of all derivatives on α-MSH-induced B16F10 cellular tyrosinase activity were shown in a dose-dependent manner. Additionally, the derivatives were exposed to diphenylpicrylhydrazyl free radical to examine their antioxidant characteristics. All derivatives showed considerable antioxidant activity, which was 2-fold higher than that of arbutin. In conclusion, the trimethoxybenzene derivatives, including MTB, ETB, MTC, and ETC exerted anti-melanogenic and antioxidant effects on α-MSH-stimulated melanogenesis, demonstrating their potential for use as novel hypopigmenting agents and antioxidants.

Keywords

Acknowledgement

This research was supported by a National Research foundation of Korea (NRF) grant funded by the Korean Government Program for Basic Science (NRF-2019R1F1A1043896).

References

  1. Huang HC, Hsieh WY, Niu YL, Chang TM (2014) Inhibitory effects of adlay extract on melanin production and cellular oxygen stress in B16F10 melanoma cells. Int J Mol Sci 15: 16665-16679. doi: 10.3390/ijms150916665 
  2. Iozumi, K, Hoganson GE, Pennella R, Everett MA, Fuller BB (1993) Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes. J Invest Dermatol 100: 806-811. doi: 10.1111/1523-1747.ep12476630 
  3. Bonaventure J, Domingues MJ, Larue L (2013) Cellular and molecular mechanisms controlling the migration of melanocytes and melanoma cells. Pigment Cell Melanoma Res 316-325. doi: 10.1111/pcmr.12080 
  4. Gilchrest BA, Park H, Eller MS, Yaar M (1996) Mechanisms of ultraviolet light-induced pigmentation. Photochem Photobiol 63: 1-10. doi:10.1111/j.1751-1097.1996.tb02988.x 
  5. Naeyaert JM, Eller M, Gordon PR, Park HY, Gilchrest BA (1991) Pigment content of cultured human melanocytes does not correlate with tyrosinase message level. Br J Dermatol Suppl 297-303. doi: 10.1111/j.1365-2133.1991.tb14161.x 
  6. Abdel-Malek Z, Swope VB, Suzuki I, Akcali C, Harriger MD, Boyce ST, Hearing VJ (1995) Mitogenic and melanogenic stimulation of normal human melanocytes by melanotropic peptides. Proc Natl Acad Sci USA 92: 1789-1793. doi: 10.1073/pnas.92.5.1789 
  7. Meyskens FL, Chau HV, Tohidian N, Buckmeier J (1997) Luminol-enhanced chemiluminescent response of human melanocytes and melanoma cells to hydrogen peroxide stress. Pigment Cell Res 10: 184-189. doi: 10.1111/j.1600-0749.1997.tb00482.x 
  8. Slominski A, Tobin DJ, ShibaharaS, Wortsman J (2004) Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 84: 1155-1228. doi: 10.1152/physrev.00044.2003 
  9. Funasaka Y, Komoto M, Ichihashi M (2000) Depigmenting effect of alpha-tocopheryl ferulate on normal human melanocytes. Pigment Cell Res 8: 170-174. doi: 10.1111/j.0893-5785.2000.130830.x 
  10. Chakraborty AK, Funasaka Y, Slominski A, Ermak G, Hwang J, Pawelek JM, Ichihashi M (1996) Production and release of proopiomelanocortin (POMC) derived peptides by human melanocytes and keratinocytes in culture: Regulation by ultraviolet B. Biochim Biophys Acta 1313: 130-138. doi: 10.1016/0167-4889(96)00063-8 
  11. Global Industry Analysts I (2021) Skin lightening agents-global market trajectory & analytics. IOP Publishing Businesswire. https://url.kr/g47pj5.Published on April 2021 
  12. Huang CH, Sung HC, Hsiao CY, Hu S, Ko YS (2013) Transdermal delivery of three vitamin C derivatives by er:YAG and carbon dioxide laser pretreatment. Lasers Med Sci 28: 807-814. doi: 10.1007/s10103-012-1151-y 
  13. Duskova J, Dusek J, Jahodar L, Poustka F (2005) Arbutin, salicin: The possibilities of their biotechnological production. Ceska Slov Farm 54(2): 78-81 
  14. Zhou H, Kepa JK, Siegel D, Miura S, Hiraki Y, Ross D (2009) Benzene metabolite hydroquinone up-regulates chondromodulin-I and inhibits tube formation in human bone marrow endothelial cells. Mol Pharmacol 76: 579-587. doi: 10.1124/mol.109.057323 
  15. Pillaiyar T, Manickam M, Namasivayam V (2017) Skin whitening agents: Medicinal chemistry perspective of tyrosinase inhibitors. J Enzyme Inhib Med Chem 32: 403-425. doi: 10.1080/14756366.2016.1256882 
  16. Pan R, Kong X, Cheng Y, Du L, Wang Z, Yuan C, Cheng J, Yuan Z, Zhang H, Liao Y (2021) 1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis. Acta Pharmacologica Sinica 42: 1769-1779. doi: 10.1038/s41401-021-00613-8 
  17. Song K, An SM, Kim M, Koh JS, Boo YC (2011) Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities. JDermatol Sci 63: 17-22. doi: 10.1016/j.jdermsci.2011.03.012 
  18. Su TR, Lin JJ, Tsai CC, Huang TK, Yang ZY, Wu MO, Zheng YQ, Su CC, Wu YJ (2013) Inhibition of melanogenesis by gallic acid: Possible involvement of the PI3K/akt, MEK/ERK and wnt/beta-catenin signaling pathways in B16F10 cells. Int J Mol Sci 14: 20443-20458. doi: 10.3390/ijms141020443 
  19. Jun H, Lee JH, Cho B, Seo W, Kim D, Cho K, Lee S (2012) p-Coumaric acid inhibition of CREB phosphorylation reduces cellular melanogenesis. Eur Food Res Technol 235: 1207-1211. doi: 10.1007/s00217-012-1830-8 
  20. Panich U, Onkoksoong T, Limsaengurai S, Akarasereenont P, Wongkajornsilp A (2012) UVA-induced melanogenesis and modulation of glutathione redox system in different melanoma cell lines: The protective effect of gallic acid. J Photochem Photobiol B: Biol 108: 16-22. doi: 10.1016/j.jphotobiol.2011.12.004 
  21. Bkowska A, Kucharska AZ, Oszmiaski J (2003) The effects of heating, UV irradiation, and storage on stability of the anthocyanin-polyphenol copigment complex. Food Chemistry 81: 349-355. doi: 10.1016/S0308-8146(02)00429-6 
  22. Kim IW, Jeong HS, Kim JK, Lee JK, Kim HR, Yun HY, Baek KJ, Kwon NS, Park KC, Kim DS (2015) Methyl gallate from acer barbinerve decreases melanin synthesis in mel-ab cells. Die Pharmazie: 70(1), 55-59. doi: 10.1691/ph.2015.4683 
  23. Choi C, Jeong HW (2020) Study on skin whitening and antioxidant effect of anemarrhenae rhizoma extract. J Physiol & Pathol Korean Med 34: 67-74. doi: 10.15188/kjopp.2020.04.34.2.67 
  24. Nairn R, Cresswell W, Nairn J (2015) Mushroom tyrosinase: A model system to combine experimental investigation of enzyme-catalyzed reactions, data handling using R, and enzyme-inhibitor structural studies. Biochem Mol Biol Educ 43: 370-376. doi: 10.1002/bmb.20887 
  25. Molagoda IMN, Choi YH, Lee S, Sung J, Lee CR, Lee HG, Lim J, Lee K, Jeon Y, Ma J, Kim G (2019) Ethanolic extract of hippocampus abdominalis exerts anti-melanogenic effects in B16F10 melanoma cells and zebrafish larvae by activating the ERK signaling pathway. Cosmetics (Basel) 7. doi: 10.3390/cosmetics7010001 
  26. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 28: 25-30. doi: 10.1016/S0023-6438(95)80008-5 
  27. Akaberi M, Emami SA, Vatani M, Tayarani-Najaran Z (2018) Evaluation of antioxidant and anti-melanogenic activity of different extracts of aerial parts of N. sintenisii in murine melanoma B16F10 cells. Iran J Pharm Res 17(1): 225-235 
  28. Micillo R, Pistorio V, Pizzo E, Panzella L, Napolitano A, D'Ischia M (2017) 2-S-lipoylcaffeic acid, a natural product-based entry to tyrosinase inhibition via catechol manipulation. Biomimetics (Basel) 2: 15. doi: 10.3390/biomimetics2030015 
  29. Kim JK, Park KT, Lee HS, Kim M, Lim YH (2012) Evaluation of the inhibition of mushroom tyrosinase and cellular tyrosinase activities of oxyresveratrol: Comparison with mulberroside A. J Enzyme Inhib Med Chem 27: 495-503. doi: 10.3109/14756366.2011.598866 
  30. Wu LH, Li P, Zhao QL, Piao JL, Jiao YF, Kadowaki M, Kondo T (2014) Arbutin, an intracellular hydroxyl radical scavenger, protects radiationinduced apoptosis in human lymphoma U937 cells. Apoptosis 19: 1654-1663. doi: 10.1007/s10495-014-1032-x. 
  31. Boo YC (2021) Arbutin as a Skin Depigmenting Agent with Antimelanogenic and Antioxidant Properties. Antioxidants (Basel) 10: 1129. doi: 10.3390/antiox10071129 
  32. Shi Y, Chen Q, Wang Q, Song K, Qiu L (2005) Inhibitory effects of cinnamic acid and its derivatives on the diphenolase activity of mushroom (agaricus bisporus) tyrosinase. Food Chemistry 92: 707-712. doi: 10.1016/j.foodchem.2004.08.031 
  33. Fang D (2002) Selective down-regulation of tyrosinase family gene TYRP1 by inhibition of the activity of melanocyte transcription factor, MITF. Nucleic Acids Research 30: 3096-3106. doi: 10.1093/nar/gkf424