Abstract
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.
Methods
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.
Results
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.
Conclusions
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.
Abbreviations:
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)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Dermatological ScienceAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The safety of hydroquinone.J Eur Acad Dermatol Venereol. 2006; 20: 781-787
- Arbutin increases the pigmentation of cultured human melanocytes through mechanisms other than the induction of tyrosianse activity.Pigment Cell Res. 1998; 11: 12-17
- Hydroquinone and its analogues in dermatology-a potential health risk.J Cos Dermatol. 2005; 4: 55-59
- The safety of hydroquinone: a dermatologist's response to the 2006 Fedral Register.J Am Acad Dermatol. 2007; 57: 854-872
- Involvement of oxidative stress in hydroquinone-induced cytotoxicity in catalase-deficient Escherichia coli mutants.Free Radic Res. 2005; 39: 1035-1041
- Structural criteria for depigmenting mechanism of arbutin.Phytothera Res. 2004; 18: 475-479
- Mechanism of its depigmenting action in human melanocyte culture.J Pharmcol Exp Ther. 1996; 276: 765-769
- Hydrolysis of arbutin to hydroqinone by human skin bacteria and its effect on antioxidant activity.J Cosmet Dermatol. 2008; 7: 189-193
- DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency.Exp Dermatol. 2005; 14: 601-608
- Tyrosinases from two different loci are expressed by normal and by transformed melanocytes.J Biol Chem. 1991; 266: 1147-1156
- 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
- A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in vitro.Anal Biochem. 2002; 305: 260-268
- 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
- H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo.J Invest Dermatol. 2005; 125: 221-229
- 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
- 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
- Approaches to identify inhibitors of melanin biosyntheses via the quality control of tyrosinase.J Invest Dermatol. 2007; 127: 751-761
- 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
- Effects of various storage conditions and alterations of antioxidant contents on chromatic aberration of hydroquinone ointment.Biol Pharm Bull. 2003; 26: 120-122
- Comparative efficacy and safety of deoxyarbutin A new tyrosinase-inhibiting agent.J Cosmet Sci. 2006; 57: 291-308
- Syntheses of alpha-arbutin-alpha-glycosides and their inhibitory effects on human tyrosinase.J Biosci Bioeng. 2005; 99: 272-276
Article info
Publication history
Published online: July 12, 2010
Accepted:
June 1,
2009
Received in revised form:
May 12,
2009
Received:
January 28,
2009
Identification
Copyright
© 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
