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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Inhibitory Effect of Sesamolin on Melanogenesis in B16F10 Cells Determined by In Vitro and Molecular Docking Analyses

Author(s): Seung-Hwa Baek, Myung-Gyun Kang and Daeui Park*

Volume 21, Issue 2, 2020

Page: [169 - 178] Pages: 10

DOI: 10.2174/1389201020666191011151123

Price: $65

Abstract

Background: Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition.

Objective: The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation.

Methods: Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina.

Results: Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol).

Conclusion: Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.

Keywords: Sesamolin, tyrosinase, melanogenesis, melanogenesis-related protein, anti-melanogenesis, docking simulation.

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[1]
Videira, I.F. dos S.; Moura, D.F.L.; Magina, S. Mechanisms regulating melanogenesis. An. Bras. Dermatol., 2013, 88(1), 76-83.
[http://dx.doi.org/10.1590/S0365-05962013000100009] [PMID: 23539007]
[2]
Briganti, S.; Camera, E.; Picardo, M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res., 2003, 16(2), 101-110.
[http://dx.doi.org/10.1034/j.1600-0749.2003.00029.x] [PMID: 12622786]
[3]
Ortonne, J-P.; Bissett, D.L. Latest insights into skin hyperpigmentation. Investig. Dermatol. Symp. Proc., 2008, pp. 10-14.
[4]
D’Mello, S.A.; Finlay, G.J.; Baguley, B.C.; Askarian-Amiri, M.E. Signaling pathways in melanogenesis. Int. J. Mol. Sci., 2016, 17(7), 1144.
[http://dx.doi.org/10.3390/ijms17071144] [PMID: 27428965]
[5]
Solano, F.Melanins. Skin pigments and much more-types, structural models, biological functions, and formation routes. New J. Sci, 2014, Article ID 498276, 28.
[6]
Algahtani, H.; Marghalani, S.; Satti, M.; Shirah, B. Levetiracetam-induced skin hyperpigmentation: An extremely rare undesirable side effect. J. Epilepsy Res., 2017, 7(2), 106-108.
[http://dx.doi.org/10.14581/jer.17016] [PMID: 29344468]
[7]
Tsukamoto, K.; Jackson, I.J.; Urabe, K.; Montague, P.M.; Hearing, V.J. A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase. EMBO J., 1992, 11(2), 519-526.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05082.x] [PMID: 1537333]
[8]
Kim, Y-J.; Uyama, H. Tyrosinase inhibitors from natural and synthetic sources: Structure, inhibition mechanism and perspective for the future. Cell. Mol. Life Sci., 2005, 62(15), 1707-1723.
[http://dx.doi.org/10.1007/s00018-005-5054-y] [PMID: 15968468]
[9]
Maeda, K.; Fukuda, M. Arbutin: Mechanism of its depigmenting action in human melanocyte culture. J. Pharmacol. Exp. Ther., 1996, 276(2), 765-769.
[PMID: 8632348]
[10]
Khemis, A.; Kaiafa, A.; Queille-Roussel, C.; Duteil, L.; Ortonne, J.P. Evaluation of efficacy and safety of rucinol serum in patients with melasma: A randomized controlled trial. Br. J. Dermatol., 2007, 156(5), 997-1004.
[http://dx.doi.org/10.1111/j.1365-2133.2007.07814.x] [PMID: 17388924]
[11]
Lee, J.; Jun, H.; Jung, E.; Ha, J.; Park, D. Whitening effect of α-bisabolol in Asian women subjects. Int. J. Cosmet. Sci., 2010, 32(4), 299-303.
[http://dx.doi.org/10.1111/j.1468-2494.2010.00560.x] [PMID: 20642768]
[12]
Castanedo-Cazares, J.P.; Lárraga-Piñones, G.; Ehnis-Pérez, A.; Fuentes-Ahumada, C.; Oros-Ovalle, C.; Smoller, B.R.; Torres-Álvarez, B. Topical niacinamide 4% and desonide 0.05% for treatment of axillary hyperpigmentation: A randomized, double-blind, placebo-controlled study. Clin. Cosmet. Investig. Dermatol., 2013, 6, 29-36.
[http://dx.doi.org/10.2147/CCID.S39246] [PMID: 23355788]
[13]
Tehranchinia, Z.; Saghi, B.; Rahimi, H. Evaluation of therapeutic efficacy and safety of tranexamic acid local infiltration in combination with topical 4% hydroquinone cream compared to topical 4% hydroquinone cream alone in patients with melasma: A split-face study. Dermatol. Res. Pract., 2018.
[http://dx.doi.org/10.1155/2018/8350317] [PMID: 30079087]
[14]
Cabanes, J.; Chazarra, S.; Garcia-Carmona, F. Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase. J. Pharm. Pharmacol., 1994, 46(12), 982-985.
[http://dx.doi.org/10.1111/j.2042-7158.1994.tb03253.x] [PMID: 7714722]
[15]
Espinal-Perez, L.E.; Moncada, B.; Castanedo-Cazares, J.P. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int. J. Dermatol., 2004, 43(8), 604-607.
[http://dx.doi.org/10.1111/j.1365-4632.2004.02134.x] [PMID: 15304189]
[16]
Nakagawa, M.; Kawai, K.; Kawai, K. Contact allergy to kojic acid in skin care products. Contact Dermat., 1995, 32(1), 9-13.
[http://dx.doi.org/10.1111/j.1600-0536.1995.tb00832.x] [PMID: 7720390]
[17]
Jeng, K.C.G.; Hou, R.C.W. Sesamin and sesamolin: Nature’s therapeutic lignans. Curr. Enzym. Inhib., 2005, 1, 11-20.
[http://dx.doi.org/10.2174/1573408052952748]
[18]
Kamal-Eldin, A.; Moazzami, A.; Washi, S. Sesame seed lignans: Potent physiological modulators and possible ingredients in functional foods & nutraceuticals. Recent Pat. Food Nutr. Agric., 2011, 3(1), 17-29.
[http://dx.doi.org/10.2174/2212798411103010017] [PMID: 21114470]
[19]
Wu, W-H.; Kang, Y-P.; Wang, N-H.; Jou, H-J.; Wang, T-A. Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in postmenopausal women. J. Nutr., 2006, 136(5), 1270-1275.
[http://dx.doi.org/10.1093/jn/136.5.1270] [PMID: 16614415]
[20]
Yamashita, K.; Iizuka, Y.; Imai, T.; Namiki, M. Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low α-tocopherol diet. Lipids, 1995, 30(11), 1019-1028.
[http://dx.doi.org/10.1007/BF02536287] [PMID: 8569430]
[21]
Miyahara, Y.; Hibasami, H.; Katsuzaki, H.; Imai, K.; Komiya, T. Sesamolin from sesame seed inhibits proliferation by inducing apoptosis in human lymphoid leukemia Molt 4B cells. Int. J. Mol. Med., 2001, 7(4), 369-371.
[http://dx.doi.org/10.3892/ijmm.7.4.369] [PMID: 11254875]
[22]
Cheng, F-C.; Jinn, T-R.; Hou, R.C.W.; Tzen, J.T.C. Neuroprotective effects of sesamin and sesamolin on gerbil brain in cerebral ischemia. Int. J. Biomed. Sci., 2006, 2(3), 284-288.
[PMID: 23674992]
[23]
Sirato-Yasumoto, S.; Katsuta, M.; Okuyama, Y.; Takahashi, Y.; Ide, T. Effect of sesame seeds rich in sesamin and sesamolin on fatty acid oxidation in rat liver. J. Agric. Food Chem., 2001, 49(5), 2647-2651.
[http://dx.doi.org/10.1021/jf001362t] [PMID: 11368649]
[24]
Mahendra Kumar, C.; Singh, S.A. Bioactive lignans from sesame (Sesamum indicum L.): evaluation of their antioxidant and antibacterial effects for food applications. J. Food Sci. Technol., 2015, 52(5), 2934-2941.
[http://dx.doi.org/10.1007/s13197-014-1334-6] [PMID: 25892793]
[25]
Srisayam, M.; Weerapreeyakul, N.; Kanokmedhakul, K. Inhibition of two stages of melanin synthesis by sesamol, sesamin and sesamolin. Asian Pac. J. Trop. Biomed., 2017, 7, 886-895.
[http://dx.doi.org/10.1016/j.apjtb.2017.09.013]
[26]
Hseu, Y-C.; Cheng, K-C.; Lin, Y-C.; Chen, C-Y.; Chou, H-Y.; Ma, D-L.; Leung, C-H.; Wen, Z-H.; Wang, H.M.H-M. Synergistic effects of linderanolide b combined with arbutin, ptu or kojic acid on tyrosinase inhibition. Curr. Pharm. Biotechnol., 2015, 16(12), 1120-1126.
[http://dx.doi.org/10.2174/1389201016666150907112819] [PMID: 26343134]
[27]
Baek, S-H.; Nam, I-J.; Kwak, H.S.; Kim, K-C.; Lee, S-H. Cellular anti-melanogenic effects of a Euryale ferox seed extract ethyl acetate fraction via the lysosomal degradation machinery. Int. J. Mol. Sci., 2015, 16(5), 9217-9235.
[http://dx.doi.org/10.3390/ijms16059217] [PMID: 25915032]
[28]
Pintus, F.; Spanò, D.; Corona, A.; Medda, R. Antityrosinase activity of Euphorbia characias extracts. Peer J, 2015, 3, e1305.
[http://dx.doi.org/10.7717/peerj.1305] [PMID: 26500815]
[29]
Pieper, U.; Eswar, N.; Davis, F.P.; Braberg, H.; Madhusudhan, M.S.; Rossi, A.; Marti-Renom, M.; Karchin, R.; Webb, B.M.; Eramian, D.; Shen, M.Y.; Kelly, L.; Melo, F.; Sali, A. MODBASE: A database of annotated comparative protein structure models and associated resources. Nucleic Acids Res., 2006, 34(Database issue), D291-D295.
[http://dx.doi.org/10.1093/nar/gkj059] [PMID: 16381869]
[30]
Vina, A. Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading Trott, Oleg; Olson, Arthur J. J. Comput. Chem., 2010, 31, 455-461.
[PMID: 19499576]
[31]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[32]
Ryazanova, A.D.; Alekseev, A.A.; Slepneva, I.A. The phenylthiourea is a competitive inhibitor of the enzymatic oxidation of DOPA by phenoloxidase. J. Enzyme Inhib. Med. Chem., 2012, 27(1), 78-83.
[http://dx.doi.org/10.3109/14756366.2011.576010] [PMID: 21534859]
[33]
Chang, T-S. An updated review of tyrosinase inhibitors. Int. J. Mol. Sci., 2009, 10(6), 2440-2475.
[http://dx.doi.org/10.3390/ijms10062440] [PMID: 19582213]
[34]
Kameyama, K.; Sakai, C.; Kuge, S.; Nishiyama, S.; Tomita, Y.; Ito, S.; Wakamatsu, K.; Hearing, V.J. The expression of tyrosinase, tyrosinase-related proteins 1 and 2 (TRP1 and TRP2), the silver protein, and a melanogenic inhibitor in human melanoma cells of differing melanogenic activities. Pigment Cell Res., 1995, 8(2), 97-104.
[http://dx.doi.org/10.1111/j.1600-0749.1995.tb00648.x] [PMID: 7659683]
[35]
Lai, X.; Wichers, H.J.; Soler-Lopez, M.; Dijkstra, B.W. Structure and function of human tyrosinase and tyrosinase-related proteins. Chemistry, 2018, 24(1), 47-55.
[http://dx.doi.org/10.1002/chem.201704410] [PMID: 29052256]
[36]
Chao, H.C.; Najjaa, H.; Villareal, M.O.; Ksouri, R.; Han, J.; Neffati, M.; Isoda, H. Arthrophytum scoparium inhibits melanogenesis through the down-regulation of tyrosinase and melanogenic gene expressions in B16 melanoma cells. Exp. Dermatol., 2013, 22(2), 131-136.
[http://dx.doi.org/10.1111/exd.12089] [PMID: 23362872]
[37]
Baek, S.H.; Lee, S.H. Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways. Exp. Dermatol., 2015, 24(10), 761-766.
[http://dx.doi.org/10.1111/exd.12765] [PMID: 26010596]
[38]
Koo, J-H.; Kim, H.T.; Yoon, H-Y.; Kwon, K-B.; Choi, I-W.; Jung, S.H.; Kim, H-U.; Park, B-H.; Park, J-W. Effect of xanthohumol on melanogenesis in B16 melanoma cells. Exp. Mol. Med., 2008, 40(3), 313-319.
[http://dx.doi.org/10.3858/emm.2008.40.3.313] [PMID: 18587269]
[39]
Kim, D-S.; Jeong, Y-M.; Park, I-K.; Hahn, H-G.; Lee, H-K.; Kwon, S-B.; Jeong, J.H.; Yang, S.J.; Sohn, U.D.; Park, K-C. A new 2-imino-1,3-thiazoline derivative, KHG22394, inhibits melanin synthesis in mouse B16 melanoma cells. Biol. Pharm. Bull., 2007, 30(1), 180-183.
[http://dx.doi.org/10.1248/bpb.30.180] [PMID: 17202683]
[40]
Jeon, J.S.; Lee, M.J.; Yoon, M.H.; Park, J-A.; Yi, H.; Cho, H-J.; Shin, H-C. Determination of arbutin, niacinamide, and adenosine in functional cosmetic products by high-performance liquid chromatography. Anal. Lett., 2014, 47, 1650-1660.
[http://dx.doi.org/10.1080/00032719.2014.883517]
[41]
Kubo, I.; Kinst-Hori, I. Flavonols from saffron flower: tyrosinase inhibitory activity and inhibition mechanism. J. Agric. Food Chem., 1999, 47(10), 4121-4125.
[http://dx.doi.org/10.1021/jf990201q] [PMID: 10552777]
[42]
Ando, H.; Kondoh, H.; Ichihashi, M.; Hearing, V.J. Approaches to identify inhibitors of melanin biosynthesis via the quality control of tyrosinase. J. Invest. Dermatol., 2007, 127(4), 751-761.
[http://dx.doi.org/10.1038/sj.jid.5700683] [PMID: 17218941]
[43]
Xiong, J.; Xiao, H.; Zhang, Z. An experimental research on different detection conditions between MTT and CCK-8. Acta Laser Biol. Sin., 2007, 16, 559.
[44]
Xu, W.; Gong, L.; Haddad, M.M.; Bischof, O.; Campisi, J.; Yeh, E.T.H.; Medrano, E.E. Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9. Exp. Cell Res., 2000, 255(2), 135-143.
[http://dx.doi.org/10.1006/excr.2000.4803] [PMID: 10694430]
[45]
Chen, H.; Weng, Q.Y.; Fisher, D.E. UV signaling pathways within the skin. J. Invest. Dermatol., 2014, 134(8), 2080-2085.
[http://dx.doi.org/10.1038/jid.2014.161] [PMID: 24759085]
[46]
Jin, M.L.; Park, S.Y.; Kim, Y.H.; Park, G.; Son, H-J.; Lee, S-J. Suppression of α-MSH and IBMX-induced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms. Int. J. Mol. Med., 2012, 29(1), 119-124.
[PMID: 21972008]
[47]
Yuan, X-H.; Yao, C.; Oh, J-H.; Park, C-H.; Tian, Y-D.; Han, M.; Kim, J.E.; Chung, J.H.; Jin, Z-H.; Lee, D.H. Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB/MITF/tyrosinase signaling. Biochem. Biophys. Res. Commun., 2016, 477(3), 336-342.
[http://dx.doi.org/10.1016/j.bbrc.2016.06.105] [PMID: 27343558]
[48]
Sun, M.; Xie, H.F.; Tang, Y.; Lin, S.Q.; Li, J.M.; Sun, S.N.; Hu, X.L.; Huang, Y.X.; Shi, W.; Jian, D. G protein-coupled estrogen receptor enhances melanogenesis via cAMP-Protein Kinase (PKA) by upregulating microphthalmia-related transcription factortyrosinase in melanoma. J. Steroid Biochem. Mol. Biol, 2017, 165(Pt B), 236-246.
[http://dx.doi.org/10.1016/j.jsbmb.2016.06.012] [PMID: 27378491]
[49]
Lee, W.R.; Shen, S.C.; Wu, P.R.; Chou, C.L.; Shih, Y.H.; Yeh, C.M.; Yeh, K.T.; Jiang, M.C. CSE1L Links cAMP/PKA and Ras/ERK pathways and regulates the expressions and phosphorylations of ERK1/2, CREB, and MITF in melanoma cells. Mol. Carcinog., 2016, 55(11), 1542-1552.
[http://dx.doi.org/10.1002/mc.22407] [PMID: 26331446]
[50]
Lee, C.S.; Jang, W.H.; Park, M.; Jung, K.; Baek, H.S.; Joo, Y.H.; Park, Y.H.; Lim, K.M. A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression. Exp. Dermatol., 2013, 22(11), 762-764.
[http://dx.doi.org/10.1111/exd.12248] [PMID: 24107097]
[51]
Johannessen, C.M.; Johnson, L.A.; Piccioni, F.; Townes, A.; Frederick, D.T.; Donahue, M.K.; Narayan, R.; Flaherty, K.T.; Wargo, J.A.; Root, D.E.; Garraway, L.A. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature, 2013, 504(7478), 138-142.
[http://dx.doi.org/10.1038/nature12688] [PMID: 24185007]
[52]
Buscà, R.; Ballotti, R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res., 2000, 13(2), 60-69.
[http://dx.doi.org/10.1034/j.1600-0749.2000.130203.x] [PMID: 10841026]

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