title: Cosmetic applications of glucitol-core containing gallotannins from a proprietary phenolic-enriched red maple (Acer rubrum) leaves extract: inhibition of melanogenesis via down-regulation of tyrosinase and melanogenic gene expression in B16F10 melanoma cells.
abstract: The red maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups attached to different positions of a 1,5-anhydro-D-glucitol core. While these glucitol-core containing gallotannins (GCGs) have reported anti-oxidant and anti-glycative effects, they have not yet been evaluated for their cosmetic applications. Herein, the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract [Maplifa™; contains ca. 45% ginnalin A (GA) along with other GCGs] were investigated using enzyme and cellular assays. The GCGs showed anti-tyrosinase activity with IC50values ranging from 101.4 to 1047.3 μM and their mechanism of tyrosinase inhibition (using GA as a representative GCG) was evaluated by chelating and computational/modeling studies. GA reduced melanin content in murine melanoma B16F10 cells by 79.1 and 56.7% (at non-toxic concentrations of 25 and 50 μM, respectively), and its mechanisms of anti-melanogenic effects were evaluated by using methods including fluorescent probe (DCF-DA), real-time PCR, and western blot experiments. These data indicated that GA was able to: (1) reduce the levels of reactive oxygen species, (2) down-regulate the expression of MITF, TYR, TRP-1, and TRP-2 gene levels in a time-dependent manner, and (3) significantly reduce protein expression of the TRP-2 gene. Therefore, the anti-melanogenic effects of red maple GCGs warrant further investigation of this proprietary natural product extract for potential cosmetic applications.
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA. hang_ma@uri.edu.
authors.forename: Hang
authors.initials: H
authors.lastname: Ma
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.|Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: DaSilva
authors.affiliation: Pre-Incubator for Innovative Drugs and Medicine, School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Zhengxi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Liangran
authors.initials: L
authors.lastname: Guo
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle Road at University City, Guangzhou, 510006, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle Road at University City, Guangzhou, 510006, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA. nseeram@uri.edu.
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
mesh_terms: D031002:Acer / Q000276:immunology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000627:therapeutic use*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000502:physiology; D008546:Melanoma, Experimental; D051379:Mice; D010636:Phenols / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*; D018515:Plant Leaves; D012878:Skin Neoplasms / Q000188:drug therapy*; D013012:Sorbitol / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D047348:Hydrolyzable Tannins; D008543:Melanins; D010636:Phenols; D010936:Plant Extracts; D013012:Sorbitol; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
keywords: Anti-melanogenic; Anti-tyrosinase; Cosmetic; Glucitol-core containing gallotannins (GCGs); Red maple (Acer rubrum); Skin-whitening