Assessment of the Effect of Arbutin Isomers and Kojic Acid on Melanin Production, Tyrosinase Activity, and Tyrosinase Expression in B16-4A5 and HMV-II Melanoma Cells

Abstract

The inhibitory effects of α-arbutin, β-arbutin, and kojic acid on melanogenesis, tyrosinase activity, and tyrosinase protein expression in mouse melanoma cells (B16-4A5) and human melanoma cells (HMV-II) were directly compared. β-Arbutin showed a stronger inhibitory effect on melanogenesis and tyrosinase expression in B16-4A5 cells than α-arbutin and kojic acid. Kojic acid showed a stronger inhibitory effect on mushroom and B16-4A5 tyrosinase activity than α-arbutin and β-arbutin. In contrast, kojic acid inhibited all of these effects more strongly than α-arbutin or β-arbutin in HMV-II cells. These results suggest that kojic acid may be used as a positive control for the inhibitory melanogenesis assay, and for tyrosinase activity and tyrosinase expression assays that use HMV-II cells. Moreover, using HMV-II cells with kojic acid as the positive control may facilitate the search for new skin-whitening agents using natural products and provide an alternative to the B16-4A5 assay.

Key words

α-arbutin - β-arbutin - kojic acid - melanin - tyrosinase

• References

• 1 Tomira Y, Maeda K, Tagami H. Mechanisms for hyperpigmentation in postinflammatory pigmentation, urticarial pigmentation and sunburn. Dermatologica 1989; 179 (Suppl. 01) 49-53
• 2 Briganti S, Camera E, Picardo M. Chemical and instrumental approaches to treat hyperpigmentation. Pigment Cell Res 2003; 16: 101-110
• 3 Chang TS. An updated review of tyrosinase inhibitors. Int J Mol Sci 2009; 10: 2440-2475
• 4 Jennifer C, Stephie CM, Abhishri SB, Shalini BU. A review on skin whitening property of plant extracts. Int J Pharm Bio Sci 2012; 3: 332-347
• 5 Maeda K, Fukuda M. In vitro effectiveness of several whitening cosmetic components in human melanocyte. J Soc Cosmet Chem 1991; 42: 361-368
• 6 Nakamura T, Seki S, Matsubara O, Ito S, Kasuga T. Specific incorporation of 4-S-cysteinylphenol into human melanoma cells. J Invest Dermatol 1988; 90: 725-728
• 7 Mitani K, Takano F, Kawabata T, Allam AE, Ota M, Takahashi T, Yahagi N, Sakurada C, Fushiya S, Ohta T. Suppression of melanin synthesis by the phenolic constituents of sappanwood (Caesalpinia sappan). Planta Med 2013; 79: 37-44
• 8 Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Inhibitory effects of alpha-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Biol Pharm Bull 2004; 27: 510-514
• 9 Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Syntheses of arbutin-alpha-glycosides and a comparison of their inhibitory effects with those of alpha-arbutin and arbutin on human tyrosinase. Chem Pharm Bull (Tokyo) 2003; 51: 798-801
• 10 Pomerantz SH. The tyrosine hydroxylase activity of mammalian tyrosinase. J Biol Chem 1966; 241: 161-168
• 11 Hwang JH, Lee BM. Inhibitory effects of plant extracts on tyrosinase, L-DOPA oxidation, and melanin synthesis. J Toxicol Environ Health A 2007; 70: 393-407
• 12 Sato K, Takahashi H, Iraha R, Toriyama M. Down-regulation of tyrosinase expression by acetylsalicylic acid in murine B16 melanoma. Biol Pharm Bull 2008; 31: 33-37
• 13 Kai H, Baba M, Okuyama T. Inhibitory effect of Cucumis sativus on melanin production in melanoma B16 cells by downregulation of tyrosinase expression. Planta Med 2008; 74: 1785-1788
• 14 Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Inhibitory effects of α-arbutin on melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model. Biol Pharm Bull 2004; 27: 510-514
• 15 Ha SK, Koketsu M, Lee K, Choi SY, Park JH, Ishihara H, Kim SY. Inhibition of tyrosinase activity by N,N-unsubstituted selenourea derivatives. Biol Pharm Bull 2005; 28: 838-840
• 16 Ohguchi K, Akao Y, Nozawa Y. Involvement of calpain in melanogenesis of mouse B16 melanoma cells. Mol Cell Biochem 2005; 275: 103-107
• 17 Hata K, Hori K, Murata J, Takahashi S. Remodeling of actin cytoskeleton in lupeol-induced B16 2F2 cell differentiation. J Biochem 2005; 138: 467-472