title: Redox-active biflavonoids from Garcinia brasiliensis as inhibitors of neutrophil oxidative burst and human erythrocyte membrane damage.
abstract: BACKGROUND
  Garcinia brasiliensis, a plant native to the Brazilian Amazon Rainforest, is used in traditional medicine to treat inflammation of the urinary tract, peptic ulcers, arthritis and other conditions.
  
  
  OBJECTIVE
  The purposes of this study were to analyze the chemical constituents of G. brasiliensis branches and leaves and to evaluate the potential of isolated compounds to act as inhibitors of both the oxidative burst of stimulated neutrophils and oxidative damage in human erythrocyte membranes to verify the antioxidant and anti-inflammatory effects of this plant.
  
  
  METHODS
  Neutrophils were isolated from the blood of healthy donors by Ficoll-Paque density gradient centrifugation. Superoxide anion and total reactive oxygen species (ROS) produced by stimulated neutrophils were measured by WST-1 reduction and luminol-enhanced chemiluminescence assays, respectively. Radical-induced lipoperoxidation and hemolysis were performed using erythrocytes from the blood of healthy donors. Compounds were isolated from G. brasiliensis branches and leaves by HPLC microfractionation, and structure elucidation of the isolated compounds was performed based on NMR and HR-MS analyses.
  
  
  RESULTS
  The biflavonoids procyanidin, fukugetin, amentoflavone and podocarpusflavone isolated from G. brasiliensis showed potent inhibitory effects on the oxidative burst of human neutrophils, inhibiting ROS production by 50% at 1 μmol L(-1). These biflavonoids also proved to be potent inhibitors of hemolysis (with 88 ± 7% inhibition at 50 µmol L(-1) for procyanidin) and lipid peroxidation in human erythrocytes, with a malondialdehyde level (a biomarker of oxidative stress) of 8.5 ± 0.3 nmol/mg Hb at 50 µmol L(-1) for procyanidin.
  
  
  CONCLUSIONS
  These findings indicate that the biflavonoids extracted from G. brasiliensis branches and leaves modulate oxidative stress via inhibition of NADPH oxidase and ROS production by stimulated human neutrophils. Furthermore, the biflavonoids exhibited potent inhibition of oxidant hemolysis and lipid peroxidation induced by AAPH in human erythrocytes. Therefore, these studies suggest the use of G. brasiliensis extract as an antioxidant and anti-inflammatory agent.
authors: Department of Organic Chemistry, Nucleus of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NUBBE), Institute of Chemistry, São Paulo State University (UNESP), P.O. Box 355, 14800-900 Araraquara, São Paulo, Brazil.
authors: Phanuel
authors: P
authors: Saroni Arwa
authors: Department of Organic Chemistry, Nucleus of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NUBBE), Institute of Chemistry, São Paulo State University (UNESP), P.O. Box 355, 14800-900 Araraquara, São Paulo, Brazil. Electronic address: marialuizaze@gmail.com.
authors: Maria Luiza
authors: ML
authors: Zeraik
authors: Department of Chemistry, School of Sciences, São Paulo State University (UNESP), P.O. Box 473, 17033-360 Bauru, São Paulo, Brazil.
authors: Valdecir Farias
authors: VF
authors: Ximenes
authors: Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), P.O. Box 502, 14801-902 Araraquara, São Paulo, Brazil.
authors: Luiz Marcos
authors: LM
authors: da Fonseca
authors: Department of Organic Chemistry, Nucleus of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NUBBE), Institute of Chemistry, São Paulo State University (UNESP), P.O. Box 355, 14800-900 Araraquara, São Paulo, Brazil.
authors: Vanderlan da Silva
authors: Vda S
authors: Bolzani
authors: Department of Organic Chemistry, Nucleus of Bioassays, Ecophysiology and Biosynthesis of Natural Products (NUBBE), Institute of Chemistry, São Paulo State University (UNESP), P.O. Box 355, 14800-900 Araraquara, São Paulo, Brazil. Electronic address: dhsilva@iq.unesp.br.
authors: Dulce Helena
authors: DH
authors: Siqueira Silva
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D029760:Garcinia / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D010636:Phenols; D017382:Reactive Oxygen Species; D013481:Superoxides
keywords: Anti-inflammatory; Antioxidant; Biflavonoids; Erythrocytes; Garcinia brasiliensis; Neutrophils