The aim of this study was to investigate the in vitro inhibitory effects of acanthoic acid (ACAN), isolated from Acanthopanax koreanum, on melanogenesis and its related enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16 melanoma cells. We found that ACAN significantly attenuates melanin synthesis and reduces the activity of intracellular tyrosinase, the rate-limiting melanogenic enzyme. Western blot analysis showed that ACAN also decreases tyrosinase, TRP-1, and TRP-2 protein expression. In addition, ACAN significantly decreased the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis. These results indicate that ACAN effectively inhibits melanin biosynthesis through down-regulation of MITF and thus could be useful as a new skin-whitening agent.
KimS., LeeJ., JungE., LeeJ., HuhS., HwangH., KimY., ParkD. (2009) 6-Benzylaminopurine stimulates melanogenesis via cAMP-independent activation of protein kinase A. Archives of Dermatological Research, 301, 253–258.
JungE., HwangW., KimS., KimY.S., KimY.S., LeeJ., ParkD. (2011) Depigmenting action of platycodin D depends on the cAMP/Rho-dependent signalling pathway. Experimental Dermatology, 20, 986–991.
4.
Leoty-OkombiS., BonnetS., RivalD., DegraveV., LinX., VogelgesangB., André-FreiV. (2013) In vitro melanogenesis inhibitory effects of N-feruloyldopamine. Journal of Cosmetic Science, 64, 133–144.
5.
KimH.J., LeeJ.H., ShinM.K., Hyun LeemK., KimY.J., LeeM.H. (2013) Inhibitory effect of Gastrodia elata extract on melanogenesis in HM3KO melanoma cells. Journal of Cosmetic Science, 64, 89–98.
6.
Hun SonK., Young HeoM. (2013) Inhibitory effects of Korean indigenous plants on tyrosinase and melanogenesis. Journal of Cosmetic Science, 64, 145–158.
7.
ChaiW.M., LiuX., HuY.H., FengH.L., JiaY.L., GuoYJ, ZhouH.T., ChenQ.X. (2013) Antityrosinase and antimicrobial activities of furfuryl alcohol, furfural and furoic acid. International Journal of Biological Macromolecules, 57C, 151–155.
8.
NguyenN.T., NguyenM.H., NguyenH.X., BuiN.K., NguyenM.T. (2013) Tyrosinase inhibitors from the wood of Artocarpus heterophyllus. Journal of Natural Products. In press, PubMed PMID: 23113717.
KhanM.T. (2012) Novel tyrosinase inhibitors from natural resources –their computational studies. Current Medicinal Chemistry, 19, 2262–2272.
11.
LiangC., LimJ.H., KimS.H., KimD.S. (2012) Dioscin: a synergistic tyrosinase inhibitor from the roots of Smilax china. Food Chemistry, 134, 1146–1148.
12.
KimS.S., HyunC.G., ChoiY.H., LeeN.H. (2013) Tyrosinase inhibitory activities of the compounds isolated from Neolitsea aciculata (Blume) Koidz. Journal of Enzyme Inhibition and Medicinal Chemistry. In press (PubMed PMID: 22468750)
13.
YoonW.J., KimM.J., KohH.B., LeeW.J., LeeM.H., HyunC.G. (2010) Effect of Korean red sea cucumber (Stichopus japonicus) on melanogenic protein expression in murine B16 melanoma. International Journal of Pharmacology, 6, 37–42.
14.
YoonW.J., KimM.J., MoonJ.Y., KangH.J., KimG.O., LeeN.H., HyunC.G. (2010) Effect of palmitoleic acid on melanogenic protein expression in murine b16 melanoma. Journal of Oleo Science, 59, 315–319.
15.
KimK.N., HamY.M., MoonJ.Y., KimM.J., JungY.H., JeonY.J., LeeN.H., KangN., YangH.M., KimD., HyunC.G. (2012) Acanthoic acid induces cell apoptosis through activation of the p38MAPK pathway in HL-60 human promyelocytic leukaemia. Food Chemistry, 135, 2112–2117.
16.
YangE.J., MoonJ.Y., LeeJ.S., KohJ., LeeN.H., HyunC.G. (2010) Acanthopanax koreanum fruit waste inhibits lipopolysaccharide-induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. Journal of Biomedicine and Biotechnology, 2010, 715739.
17.
YenF.L., WangM.C., LiangC.J., LeeC.W. (2012) Melanogenesis Inhibitor(s) from Phyla nodiflora extract. Evidence-based Complementary and Alternative Medicine, 2012, 867494.
18.
BertolottoC., BilleK., OrtonneJ.P., BallottiR. (1996) 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, Journal of Cell Biology, 134, 747–755.
19.
KimD.C., RhoS.H., ShinJ.C., ParkH.H., KimD. (2011) Inhibition of melanogenesis by 5,7-dihydroxyflavone (chrysin) via blocking adenylyl cyclase activity, Biochemical and Biophysical Research Communications, 411, 121–125.
