Browse > Article
http://dx.doi.org/10.4062/biomolther.2013.032

Hesperidin Suppresses Melanosome Transport by Blocking the Interaction of Rab27A-Melanophilin  

Kim, Bora (Enprani Co., Ltd. R&D Center of Skin Science and Cosmetics)
Lee, Jee-Young (Bioinformatics & Molecular Design Research Center)
Lee, Ha-Yeon (Department of Genetic Engineering, Graduate School of Biotechnology and Skin Biotechnology Center, Kyung Hee University)
Nam, Ky-Youb (Bioinformatics & Molecular Design Research Center)
Park, JongIl (Department of Genetic Engineering, Graduate School of Biotechnology and Skin Biotechnology Center, Kyung Hee University)
Lee, Su Min (Enprani Co., Ltd. R&D Center of Skin Science and Cosmetics)
Kim, Jin Eun (Enprani Co., Ltd. R&D Center of Skin Science and Cosmetics)
Lee, Joo Dong (Enprani Co., Ltd. R&D Center of Skin Science and Cosmetics)
Hwang, Jae Sung (Department of Genetic Engineering, Graduate School of Biotechnology and Skin Biotechnology Center, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.21, no.5, 2013 , pp. 343-348 More about this Journal
Abstract
We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.
Keywords
Hesperidin; Melanosome transport; Rab27A; Melanophilin; Pigmented reconstructed epidermis model;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Vallejo, F., Larrosa, M., Escudero, E., Zafrilla, M. P., Cerda, B., Boza, J., Garcia-Conesa, M. T., Espin, J. C. and Tomas-Barberan, F. A. (2010) Concentration and solubility of flavanones in orange beverages affect their bioavailability in humans. J. Agric. Food Chem. 58, 6516-6524.   DOI   ScienceOn
2 Vieth, M., Hirst, J. D. and Brooks, C. L. 3rd (1998) Do active site conformations of small ligands correspond to low free-energy solution structures? J. Comput. Aided Mol. Des. 12, 563-572.   DOI   ScienceOn
3 Wu, G., Robertson, D. H., Brooks, C. L. 3rd and Vieth, M. (2003) Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm. J. Comput. Chem. 24, 1549-1562.   DOI   ScienceOn
4 Yamaguchi, Y., Brenner, M. and Hearing, V. J. (2007) The regulation of skin pigmentation. J. Biol. Chem. 282, 27557-27561.   DOI   ScienceOn
5 Yoshida-Amano, Y., Hachiya, A., Ohuchi, A., Kobinger, G. P., Kitahara, T., Takema, Y. and Fukuda, M. (2012) Essential role of RAB27A in determining constitutive human skin color. PLoS One 7, e41160.   DOI
6 Hou, M., Man, M., Man, W., Zhu, W., Hupe, M., Park, K., Crumrine, D., Elias, P. M. and Man, M. Q. (2012) Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin. Exp. Dermatol. 21, 337-340.   DOI   ScienceOn
7 Hume, A. N. and Seabra, M. C. (2011) Melanosomes on the move: a model to understand organelle dynamics. Biochem. Soc. Trans. 39, 1191-1196.   DOI   ScienceOn
8 Kuroda, T. S. and Fukuda, M. (2004) Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Nat. Cell. Biol. 6, 1195-1203.   DOI   ScienceOn
9 Kuroda, T. S., Itoh, T. and Fukuda, M. (2005) Functional analysis of slac2-a/melanophilin as a linker protein between Rab27A and myosin Va in melanosome transport. Methods Enzymol. 403, 419-431.   DOI   ScienceOn
10 Rajnarayana, K., Prabhakar, M. C. and Krishna, D. R. (2001) Influence of rice bran oil on serum lipid peroxides and lipids in human subjects. Indian J. Physiol. Pharmacol. 45, 442-444.
11 Saiprasad, G., Chitra, P., Manikandan, R. and Sudhandiran, G. (2013) Hesperidin alleviates oxidative stress and downregulates the expressions of proliferative and inflammatory markers in azoxymethane-induced experimental colon carcinogenesis in mice. Inflamm. Res. 62, 425-440.   DOI   ScienceOn
12 Siegrist, W. and Eberle, A. N. (1986) In situ melanin assay for MSH using mouse B16 melanoma cells in culture. Anal. Biochem. 159, 191-197.   DOI   ScienceOn
13 Tanaka, T., Tanaka, T., Tanaka, M. and Kuno, T. (2012) Cancer chemoprevention by citrus pulp and juices containing high amounts of beta-cryptoxanthin and hesperidin. J. Biomed. Biotechnol. 2012, 516981.
14 Thong, H. Y., Jee, S. H., Sun, C. C. and Boissy, R. E. (2003) The patterns of melanosome distribution in keratinocytes of human skin as one determining factor of skin colour. Br. J. Dermatol. 149, 498-505.   DOI   ScienceOn
15 Boissy, R. E. (2003) Melanosome transfer to and translocation in the keratinocyte. Exp. Dermatol. 12 Suppl 2, 5-12.   DOI   ScienceOn
16 Cazarolli, L. H., Zanatta, L., Alberton, E. H., Figueiredo, M. S., Folador, P., Damazio, R. G., Pizzolatti, M. G. and Silva, F. R. (2008) Flavonoids: prospective drug candidates. Mini Rev. Med. Chem. 8, 1429-1440.   DOI   ScienceOn
17 Chang, H., Choi, H., Joo, K. M., Kim, D. and Lee, T. R. (2012) Manassantin B inhibits melanosome transport in melanocytes by disrupting the melanophilin-myosin Va interaction. Pigment Cell Melanoma Res. 25, 765-772.   DOI   ScienceOn
18 Elavarasan, J., Velusamy, P., Ganesan, T., Ramakrishnan, S. K., Rajasekaran, D. and Periandavan, K. (2012) Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart. J. Pharm. Pharmacol. 64, 1472-1482.   DOI   ScienceOn
19 Fukuda, M., Kuroda, T. S. and Mikoshiba, K. (2002) Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. J. Biol. Chem. 277, 12432-12436.   DOI   ScienceOn
20 Fukuda, M. (2002) Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A. J. Biol. Chem. 277, 40118-40124.   DOI   ScienceOn
21 Ghorbani, A., Nazari, M., Jeddi-Tehrani, M. and Zand, H. (2012) The citrus flavonoid hesperidin induces p53 and inhibits NF-kappaB activation in order to trigger apoptosis in NALM-6 cells: involvement of PPARgamma-dependent mechanism. Eur. J. Nutr. 51, 39-46.
22 Hakozaki, T., Minwalla, L., Zhuang, J., Chhoa, M., Matsubara, A., Miyamoto, K., Greatens, A., Hillebrand, G. G., Bissett, D. L. and Boissy, R. E. (2002) The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br. J. Dermatol. 147, 20-31.   DOI   ScienceOn
23 Hirokawa, N. and Noda, Y. (2008) Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics. Physiol. Rev. 88, 1089-1118.   DOI   ScienceOn
24 Ando, H., Niki, Y., Ito, M., Akiyama, K., Matsui, M. S., Yarosh, D. B. and Ichihashi, M. (2012) Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. J. Invest. Dermatol. 132, 1222-1229.   DOI   ScienceOn