Abstract
Intracellular cAMP stimulates microphthalmia-associated transcription factor (MITF) induction in melanocytes through cAMP-responsive element binding protein (CREB), which plays a pivotal role in the gene expression of tyrosinase for melanin biosynthesis. In the present study, saucerneol D as a lignan constituent of Saururus chinensis (Saururaceae family) efficiently inhibited melanin production with IC50 values of 188–297 nM in B16 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH) or other cAMP elevators. Moreover, saucerneol D down-regulated α-MSH-induced gene expression of tyrosinase at the transcription level in B16 cells, but it did not directly inhibit the catalytic activity of cell-free tyrosinase. As to the molecular basis of hypopigmenting action, saucerneol D inhibited α-MSH-induced phosphorylation of CREB in the cells, and sequentially suppressed MITF induction. Taken together, this study provides saucerneol D down-regulated the gene expression of tyrosinase, resulting in the inhibition of cAMP-induced melanin biosynthesis, and suggests pharmacological potential of the lignan structure in skin hyperpigmentation.
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Ao, Y., Park, H. Y., Olaizola-Horn, S., and Gilchrest, B. A., Activation of cAMP-dependent protein kinase is required for optimal α-melanocyte-stimulating hormone-induced pigmentation. Exp. Cell Res., 244, 117–124 (1998).
Bertolotto, C., Bille, K., Ortonne, J. P., and 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., 134, 747–755 (1996).
Bertolotto, C., Abbe, P., Hemesath, T. J., Bille, K., Fisher, D. E., Ortonne, J. P., and Ballotti, R., Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J. Cell Biol., 142, 827–835 (1998).
Buscà, R. and Ballotti, R., Cyclic AMP, a key messenger in the regulation of skin pigmentation. Pigment Cell Res., 13, 60–69 (2000).
Cho, Y., Kim, K. H., Shim, J. S., and Hwang, J. K., Inhibitory effects of macelignan isolated from Myristica fragrans HOUTT. on melanin biosynthesis. Biol. Pharm. Bull., 31, 986–989 (2008).
Hirata, N., Naruto, S., Ohguchi, K., Akao, Y., Nozawa, Y., Iinuma, M., and Matsuda, H., Mechanism of the melanogenesis stimulation activity of (−)-cubebin in murine B16 melanoma cells. Bioorg. Med. Chem., 15, 4897–4902 (2007).
Hummler, E., Cole, T. J., Blendy, J. A., Ganss, R., Aguzzi, A., Schmid, W., Beermann, F., and Schütz, G., Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc. Natl. Acad. Sci. U. S. A., 91, 5647–5651 (1994).
Hwang, B. Y., Lee, J. H., Nam, J. B., Hong, Y. S., and Lee, J. J., Lignans from Saururus chinensis inhibiting the transcription factor NF-κB. Phytochemistry, 64, 765–771 (2003).
Kim, K. H., Moon, E., Kim, S. Y., and Lee, K. R., Lignans from the tuber-barks of Colocasia antiquorum var. esculenta and their antimelanogenic activity. J. Agric. Food Chem., 58, 4779–4785 (2010).
Kim, K. S., Kim, J. A., Eom, S. Y., Lee, S. H., Min, K. R., and Kim, Y., Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression. Pigment Cell Res., 19, 90–98 (2006).
Kim, Y. M., Yun, J., Lee, C. K., Lee, H., Min, K. R., and Kim, Y., Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action. J. Biol. Chem., 277, 16340–16344 (2002).
Kumar, C. M., Sathisha, U. V., Dharmesh, S., Rao, A. G., and Singh, S. A., Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis. Biochimie, 93, 562–569 (2011).
Le Pape, E., Wakamatsu, K., Ito, S., Wolber, R., and Hearing, V. J., Regulation of eumelanin/pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor. Pigment Cell Melanoma Res., 21, 477–486 (2008).
Lee, Y. K., Seo, C. S., Lee, C. S., Lee, K. S., Kang, S. J., Jahng, Y., Chang, H. W., and Son, J. K., Inhibition of DNA topoisomerases I and II and cytotoxicity by lignans from Saururus chinensis. Arch. Pharm. Res., 32, 1409–1415 (2009).
Li, G., Ju, H. K., Chang, H. W., Jahng, Y., Lee, S. H., and Son, J. K., Melanin biosynthesis inhibitors from the bark of Machilus thunbergii. Biol. Pharm. Bull., 26, 1039–1041 (2003).
Maeda, K. and Fukuda, M., Arbutin: mechanism of its depigmenting action in human melanocyte culture. J. Pharmacol. Exp. Ther., 276, 765–769 (1996).
Moon, T. C., Kim, J. C., Song, S. E., Suh, S. J., Seo, C. S., Kim, Y. K., Jin, M., Yang, J. H., Son, J. K., Jahng, Y., Kim, C. H., and Chang, H. W., Saucerneol D, a naturally occurring sesquilignan, inhibits LPS-induced iNOS expression in Raw 264.7 cells by blocking NF-κB and MAPK activation. Int. Immunopharmacol., 8, 1395–1400 (2008).
Oh, K. S., Choi, Y. H., Ryu, S. Y., Oh, B. K., Seo, H. W., Yon, G. H., Kim, Y. S., and Lee, B. H., Cardiovascular effects of lignans isolated from Saururus chinensis. Planta Med., 74, 233–238 (2008).
Schweikardt, T., Olivares, C., Solano, F., Jaenicke, E., GarcÍa-Borrón, J. C., and Decker, H., A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations. Pigment Cell Res., 20, 394–401 (2007).
Seo, C. S., Lee, W. H., Chung, H. W., Chang, E. J., Lee, S. H., Jahng, Y., Hwang, B. Y., Son, J. K., Han, S. B., and Kim, Y., Manassantin A and B from Saururus chinensis inhibiting cellular melanin production. Phytother. Res., 23, 1531–1536 (2009).
Shibahara, S., Yasumoto, K., Amae, S., Udono, T., Watanabe, K., Saito, H., and Takeda, K., Regulation of pigment cellspecific gene expression by MITF. Pigment Cell Res., 13Suppl 8, 98–102 (2000).
Slominski, A., Tobin, D. J., Shibahara, S., and Wortsman, J., Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol. Rev., 84, 1155–1228 (2004).
Solano, F., Briganti, S., Picardo, M., and Ghanem, G., Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res., 19, 550–571 (2006).
Sung, S. H., Huh, M. S., and Kim, Y. C., New tetrahydrofuran-type sesquilignans of Saururus chinensis root. Chem. Pharm. Bull. (Tokyo), 49, 1192–1194 (2001).
Yasumoto, K., Yokoyama, K., Takahashi, K., Tomita, Y., and Shibahara, S., Functional analysis of microphthalmiaassociated transcription factor in pigment cell-specific transcription of the human tyrosinase family genes. J. Biol. Chem., 272, 503–509 (1997).
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Yun, J.Y., Roh, E., Son, JK. et al. Effect of saucerneol D on melanin production in cAMP-elevated melanocytes. Arch. Pharm. Res. 34, 1339–1345 (2011). https://doi.org/10.1007/s12272-011-0814-8
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DOI: https://doi.org/10.1007/s12272-011-0814-8