title: Inhibitory effect of GB-2a (I3-naringenin-II8-eriodictyol) on melanogenesis.
abstract: BACKGROUND
  GB-2a is a I3-naringenin-II8-eriodictyol compound isolated from Garcinia gardneriana (Planchon & Triana) Zappi, a plant used in folk medicine for the treatment of skin disorders.
  
  
  OBJECTIVE
  In the search for new depigmenting agents, this study was carried out to investigate the in vitro effects of GB-2a isolated from G. gardneriana (Planchon & Triana) Zappi in B16F10 melanoma cells.
  
  
  METHODS
  The effects of GB-2a were evaluated through determination of melanin biosynthesis in B16F10 melanoma cells in comparison with the reference drug kojic acid (500µM). In parallel, the GB-2a effect was assessed in a cell viability assay. Mushroom tyrosinase activity assays were conducted to verify the effect of this enzyme. In order to ascertain the nature of enzyme inhibition on tyrosinase, kinetics analysis of the GB-2a was performed with L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) substrates.
  
  
  RESULTS
  The results showed that GB-2a biflavonoid significantly inhibited the melanin content, without reducing cell viability. GB-2a also showed a strong antityrosinase activity in the mushroom tyrosinase assay. GB-2a inhibited the tyrosinase activity, exerting a mixed inhibition. For the L-tyrosine substrate the inhibition was in non-competitive mode and for L-DOPA it was in uncompetitive mode.
  
  
  CONCLUSIONS
  GB-2a biflavonoid promoted inhibition on tyrosinase activity and reduced melanin biosynthesis in B16F10 cells, which suggests great potential for medical and cosmetic uses as a depigmenting agent.
authors: Department of Pharmaceutical Sciences, Federal University of Parana, CEP 80210-170, Curitiba, PR, Brazil.
authors: Patrícia Mazureki
authors: PM
authors: Campos
authors: Department of Pharmacology, Federal University of Parana, CEP 81530-900, Curitiba, PR, Brazil.
authors: Arthur Silveira
authors: AS
authors: Prudente
authors: Department of Pharmacology, Federal University of Parana, CEP 81530-900, Curitiba, PR, Brazil.
authors: Cíntia Delai da Silva
authors: CD
authors: Horinouchi
authors: Investigation Centre of Pharmaceutical Chemistry, University of Itajai Valley, CEP 88302-202, Itajai, SC, Brazil.
authors: Valdir
authors: V
authors: Cechinel-Filho
authors: Department of Biological Sciences, State University of Ponta Grossa, CEP 84030-900, Ponta Grossa, PR, Brazil.
authors: Giovani Marino
authors: GM
authors: Fávero
authors: Department of Pharmacology, Federal University of Parana, CEP 81530-900, Curitiba, PR, Brazil.
authors: Daniela Almeida
authors: DA
authors: Cabrini
authors: Department of Pharmacology, Federal University of Parana, CEP 81530-900, Curitiba, PR, Brazil. Electronic address: michelotuki@yahoo.com.br.
authors: Michel Fleith
authors: MF
authors: Otuki
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D029760:Garcinia; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves
chemical_list: D044950:Flavanones; D008543:Melanins; D010936:Plant Extracts; C005273:naringenin
keywords: Biflavonoid; Garcinia gardneriana; Hyperpigmentation; I3-Naringenin-II8-eriodictyol; I3-Naringenin-II8-eriodictyol (PubChem CID: 176988); Melanin; Tyrosinase inhibition