Volume 39, Issue 3 p. 259-270
Research Communication

In vitro and in vivo studies disclosed the depigmenting effects of gallic acid: A novel skin lightening agent for hyperpigmentary skin diseases

K. J. Senthil Kumar

K. J. Senthil Kumar

Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan

K. J. Senthil Kumar and M. Gokila Vani have contributed equally.

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M. Gokila Vani

M. Gokila Vani

Graduate Institute of Nutrition, College of Health Care, China Medical University, Taichung, Taiwan

K. J. Senthil Kumar and M. Gokila Vani have contributed equally.

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Sheng-Yang Wang

Sheng-Yang Wang

Department of Forestry, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung, Taiwan

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Jiunn-Wang Liao

Jiunn-Wang Liao

Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan

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Li-Sung Hsu

Li-Sung Hsu

Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

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Hsin-Ling Yang

Corresponding Author

Hsin-Ling Yang

Graduate Institute of Nutrition, College of Health Care, China Medical University, Taichung, Taiwan

Tel.: +886-4-22053366 ext 7503; Fax: +886-4-22062891

Hsin-Ling Yang, Graduate Institute of Nutrition, China Medical University, Taichung, Taiwan

You-Cheng Hseu, Department of Cosmeceutics, College of Pharmacy, Taichung, Taiwan

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You-Cheng Hseu

Corresponding Author

You-Cheng Hseu

Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan

Hsin-Ling Yang, Graduate Institute of Nutrition, China Medical University, Taichung, Taiwan

You-Cheng Hseu, Department of Cosmeceutics, College of Pharmacy, Taichung, Taiwan

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First published: 16 January 2013
Citations: 55

Abstract

Gallic acid (GA) is a phenolic compound, which has been reported to suppress melanogenesis in melanoma cells. However, the molecular mechanism underlying this inhibitory effect was poorly understood. In this article, we revealed that GA down-regulated melanogenic regulatory genes including tyrosinase, tyrosinase related protein-1 (TRP-1), and dopachrome tatamerase (Dct) expression at transcriptional and translational level. In addition, GA effectively suppressed the microphthalmia-associated transcription factor (MITF) expression by down-regulating the cAMP-mediated PKA/CREB signaling cascades. To delineate the inhibition of MITF by GA, the activation of extracellular signal-regulated protein kinase (ERK) and AKT was investigated. GA caused significant increase of ERK and AKT phosphorylation, while ERK (PD98059) or AKT (LY294002) inhibitor prevents their phosphorylation and increased melanin biosynthesis. In addition, pre-treatment of MITF-siRNA significantly reduced melanin production from 100 to 40%, and even decreased into 10% by combination treatment with GA. Furthermore, UVB-induced hyperpigmentation in the mice skin was significantly rescued by topical application of GA for 4 weeks. Immunohistochemical analyses also confirmed that GA significantly inhibited melanin production followed by the down-regulation of MITF, tyrosinase and their regulatory proteins. In addition, when compared with control zebrafish, GA caused a remarkable inhibition on the endogenous pigmentation in the zebrafish. Results presented in this study strongly suggest that GA is an effective de-pigmenting or skin lightening cosmetics for topical application. © 2012 BioFactors, 2013