Dioscin Derived from Solanum melongena L. "Usukawamarunasu" Attenuates α-MSH-Induced Melanogenesis in B16 Murine Melanoma Cells via Downregulation of Phospho-CREB and MITF.
This study aimed to chemically isolate and explore an antimelanogenesis inducer in extracts of Solanum melongena L. "Usukawamarunasu" eggplant. We successfully identified dioscin ([25R]-Spirost-5-en-3β-yl) 2-O-(6-deoxy-α-L-mannopyranosyl) - 4-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranoside] in the plant, and examined the effects of α-melanocyte-stimulating hormone (MSH)-induced melanogenesis in B16 murine melanoma cells by this plant-derived dioscin. Immunoblot analysis suggested that dioscin reduced the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2, resulting in inhibition of intracellular production of melanin. In addition, dioscin caused reduction of phosphorylated cAMP-responsive element binding protein 1 transcription factors (CREB), which led to a reduction of microphthalmia-related transcription factor (MITF) in α-MSH-stimulated cells, but did not affect phosphorylation of extracellular signal-regulated kinase. Furthermore, dioscin significantly downregulated the expression of tyrosinase, TRP-1, and TRP-2, which led to the reduction of α-MSH-induced melanogenesis in B16 cells. These results suggest that dioscin may decrease the level of MITF via inhibition of phosphorylation of CREB in α-MSH-induced melanogenesis in B16 cells.
College of Science and Technology, Nihon Univ, Chiyoda-ku, P.O. Box 101-0062, Tokyo, Japan.
Atsuyoshi
A
Nishina
College of Science and Technology, Nihon Univ, Chiyoda-ku, P.O. Box 101-0062, Tokyo, Japan.
Kodai
K
Ebina
College of Science and Technology, Nihon Univ, Chiyoda-ku, P.O. Box 101-0062, Tokyo, Japan.
Motohiko
M
Ukiya
College of Science and Technology, Nihon Univ, Chiyoda-ku, P.O. Box 101-0062, Tokyo, Japan.
Makoto
M
Fukatsu
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu Univ, P.O. Box 501-1112, Gifu, Japan.
Mamoru
M
Koketsu
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu Univ, P.O. Box 501-1112, Gifu, Japan.
Masayuki
M
Ninomiya
Dept. of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata Univ, P.O. Box 990-2332, Yamagata, Japan.
Daisuke
D
Sato
Natl. Inst. of Infectious Diseases, Musashimurayama-shi, P.O. Box 208-0011, Tokyo, Japan.
Hirokazu
H
Kimura
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D032323:Solanum melongena / Q000737:chemistry*; D000521:alpha-MSH / Q000378:metabolism*
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D010936:Plant Extracts; C019357:dioscin; D000521:alpha-MSH; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D004144:Diosgenin
Solanum melongena L; cAMP-responsive element binding protein 1 transcription factors; dioscin; melanogenesis; microphthalmia-related transcription factor