title: In vitro and in vivo studies disclosed the depigmenting effects of gallic acid: a novel skin lightening agent for hyperpigmentary skin diseases.
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.
authors: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
authors: K J Senthil
authors: KJ
authors: Kumar
authors: M Gokila
authors: MG
authors: Vani
authors: Sheng-Yang
authors: SY
authors: Wang
authors: Jiunn-Wang
authors: JW
authors: Liao
authors: Li-Sung
authors: LS
authors: Hsu
authors: Hsin-Ling
authors: HL
authors: Yang
authors: You-Cheng
authors: YC
authors: Hseu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005707:Gallic Acid / Q000494:pharmacology*; D017495:Hyperpigmentation / Q000188:drug therapy* / Q000378:metabolism*; D007150:Immunohistochemistry; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering; D005707:Gallic Acid; D014442:Monophenol Monooxygenase