Research Article| Volume 55, ISSUE 3, P179-184, September 2009

Effects of hydroquinone and its glucoside derivatives on melanogenesis and antioxidation: Biosafety as skin whitening agents


      Background and objective

      The biosafety of hydroquinone and its derivatives as skin whitening agent remains controversial. Here, we investigated the effects of hydroquinone, arbutin, and deoxyarbutin (d-arb) on melanogenesis and antioxidation using cultured melan-a melanocytes in the presence or absence of ultraviolet A (UVA)-induced oxidative stress and determined whether d-arb enables to be an alterative to hydroquinone and arbutin for skin whitening use.


      d-arb was synthesized in this study by removing all hydroxyl groups from the glucose side-chain of arbutin. Tyrosinase activity was measured by 14C-tyrosine incorporation, the intracellular reactive oxygen species (ROS) level was monitored by H2DCFDA fluorescence labeling, and the cell viability was determined by MTT assay in murine melan-a melanocytes treated with hydroquinone, arbutin and deoxyarbutin in the presence or absence of UVA-induced oxidative stress.


      The cytotoxicity of hydroquinone and arbutin except for d-arb was increased while the cells exposed to a nontoxic dose (3 J/cm2) of UVA irradiation. Suppressed ROS generation was noted by the treatment of d-arb to compare with arbutin and hydroquinone. All three compounds had a similar inhibition on tyrosinase activity in dose-dependent manners with two- to three-fold decreases over the untreated control. There was no change in expression of tyrosinase protein in cells treated with arbutin or hydroquinone, but a decreased protein expression of tyrosinase was seen in deoxyarbutin-treated cells.


      Deoxyarbutin exerts potent tyrosinase inhibition, lessened cytotoxicity, and certain antioxidation potential, may serve as an effective and safe alternative to hydroquinone for use in skin whitening.


      d-Arb (deoxyarbutin), ROS (reactive oxygen species), 8mop (8-methoxypsoralen), MTT (methyl thiazole tetrazolium), H2DCFDA (2′,7′-dichlorodihydrofluorescein diacetate), PMA (phorbol 12-myristate 13-acetate), D-PBS (Dulbecco's phosphate buffered saline), UVA (ultraviolet A)


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        • Nordlund J.J.
        • Grimes P.E.
        • Ortonnes J.P.
        The safety of hydroquinone.
        J Eur Acad Dermatol Venereol. 2006; 20: 781-787
        • Nakajima M.
        • Shinoda I.
        • Fukuwatari Y.
        • Hayasawa H.
        Arbutin increases the pigmentation of cultured human melanocytes through mechanisms other than the induction of tyrosianse activity.
        Pigment Cell Res. 1998; 11: 12-17
        • Westerhof W.
        • Kooyers T.J.
        Hydroquinone and its analogues in dermatology-a potential health risk.
        J Cos Dermatol. 2005; 4: 55-59
        • Levitt J.
        The safety of hydroquinone: a dermatologist's response to the 2006 Fedral Register.
        J Am Acad Dermatol. 2007; 57: 854-872
        • Horita M.
        • Wang D.H.
        • Tsutsui K.
        • et al.
        Involvement of oxidative stress in hydroquinone-induced cytotoxicity in catalase-deficient Escherichia coli mutants.
        Free Radic Res. 2005; 39: 1035-1041
        • Hori I.
        • Nihei K.
        • Kubo I.
        Structural criteria for depigmenting mechanism of arbutin.
        Phytothera Res. 2004; 18: 475-479
        • Maeda K.
        • Arbtuin F.M.
        Mechanism of its depigmenting action in human melanocyte culture.
        J Pharmcol Exp Ther. 1996; 276: 765-769
        • Bang S.H.
        • Han S.J.
        • Kim D.H.
        Hydrolysis of arbutin to hydroqinone by human skin bacteria and its effect on antioxidant activity.
        J Cosmet Dermatol. 2008; 7: 189-193
        • Boissy R.E.
        • Visscher M.
        • deLong M.A.
        DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency.
        Exp Dermatol. 2005; 14: 601-608
        • Jimenez M.
        • Tsukamoto K.
        • Hearing V.J.
        Tyrosinases from two different loci are expressed by normal and by transformed melanocytes.
        J Biol Chem. 1991; 266: 1147-1156
        • Bennet D.C.
        • Cooper P.J.
        • Hart I.R.
        A line of non-tumorigenic moouse melanocytes, syngeneic with the B16 melanoma and requiring a tumor promoter for growth.
        Int J Cancer. 1987; 39: 414-418
        • Lei T.C.
        • Virador V.M.
        • Vieira W.D.
        • Hearing V.J.
        A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro.
        Anal Biochem. 2002; 305: 260-268
        • Gen J.
        • Tang W.
        • Wan X.
        • Zhou Q.
        • Wang X.J.
        • Shen P.
        • et al.
        Photoprotection of bacterial-derived melanin against ultraviolet A-induced cell death and its potential application as an active sunscreen.
        J Eur Acad Dermatol Venereol. 2008; 22: 852-858
        • Shin M.H.
        • Rhie G.E.
        • Kim Y.K.
        • Park C.H.
        • Cho K.H.
        • Kim K.H.
        • et al.
        H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo.
        J Invest Dermatol. 2005; 125: 221-229
        • Lei T.C.
        • Virador V.
        • Yasumoto K.
        • Vieira W.D.
        • Toyofuku K.
        • Hearing V.J.
        Stimulation of melanblast pigmentation by 8-methoxypsoralen: the involvement of microphthalmia-associated transcription factor, the protein kinase A signal pathway, and proteasome-mediated degradation.
        J Invest Dermatol. 2002; 119: 1341-1349
        • Tadokoro T.
        • Rouzaud F.
        • Itami S.
        • et al.
        The inhibitory effects of androgen and sex-hormone-binding globulin on the intracellular cAMP level and tyrosinase activity of normal human melanocytes.
        Pigment Cell Res. 2003; 16: 190-197
        • Ando H.
        • Kondoh H.
        • Ichihashi M.
        • Hearing V.J.
        Approaches to identify inhibitors of melanin biosyntheses via the quality control of tyrosinase.
        J Invest Dermatol. 2007; 127: 751-761
        • Zhu W.
        • Gao J.
        The use of botanical extracts as topical skin-lightening agents for the improvement of skin pigmentation disorders.
        J Invest Dermatol Symp Proc. 2008; 13: 20-24
        • Matsubayashi T.
        • Sakaeda T.
        • Kita T.
        • et al.
        Effects of various storage conditions and alterations of antioxidant contents on chromatic aberration of hydroquinone ointment.
        Biol Pharm Bull. 2003; 26: 120-122
        • Hamed S.H.
        • Sirwiriyanont P.
        • deLong M.A.
        • et al.
        Comparative efficacy and safety of deoxyarbutin A new tyrosinase-inhibiting agent.
        J Cosmet Sci. 2006; 57: 291-308
        • Sugimoto K.
        • Nomura K.
        • Nishimura T.
        • et al.
        Syntheses of alpha-arbutin-alpha-glycosides and their inhibitory effects on human tyrosinase.
        J Biosci Bioeng. 2005; 99: 272-276