title: Wayanin and guaijaverin, two active metabolites found in a Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh) (Myrtaceae) antimalarial decoction from the Wayana Amerindians.
abstract: BACKGROUND
  Psidium acutangulum Mart. ex DC is a small tree used by the Wayana Amerindians from the Upper-Maroni in French Guiana for the treatment of malaria.
  
  
  OBJECTIVE
  In a previous study, we highlighted the in vitro antiplasmodial, antioxidant and anti-inflammatory potential of the traditional decoction of P. acutangulum aerial parts. Our goal was then to investigate on the origin of the biological activity of the traditional remedy, and eventually characterize active constituents.
  
  
  METHODS
  Liquid-liquid extractions were performed on the decoction, and the antiplasmodial activity evaluated against chloroquine-resistant FcB1 ([(3)H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains, and on a chloroquine sensitive NF54 ([(3)H]-hypoxanthine bioassay) P. falciparum strain. The ethyl acetate fraction (D) was active and underwent bioguided fractionation. All the isolated compounds were tested on P. falciparum FcB1 strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) of the ethyl acetate fraction and of an anti-Plasmodium active compound, was concurrently assessed on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the fractions and pure compounds was measured on VERO cells, L6 mammalian cells, PBMCs, and RAW cells.
  
  
  RESULTS
  Fractionation of the ethyl acetate soluble fraction (IC50 ranging from 3.4 to <1µg/mL depending on the parasite strain) led to the isolation of six pure compounds: catechin and five glycosylated quercetin derivatives. These compounds have never been isolated from this plant species. Two of these compounds (wayanin and guaijaverin) were found to be moderately active against P. falciparum FcB1 in vitro (IC50 5.5 and 6.9µM respectively). We proposed the name wayanin during public meetings organized in June 2015 in the Upper-Maroni villages, in homage to the medicinal knowledge of the Wayana population. At 50µg/mL, the ethyl acetate fraction (D) significantly inhibited IL-1β secretion (-46%) and NO production (-21%), as previously observed for the decoction. The effects of D and guiajaverin (4) on the secretion of other cytokines or NO production were not significant.
  
  
  CONCLUSIONS
  The confirmed antiplasmodial activity of the ethyl acetate soluble fraction of the decoction and of the isolated compounds support the previous results obtained on the P. acutangulum decoction. The antiplasmodial activity might be due to a mixture of moderately active non-toxic flavonoids. The anti-inflammatory activities were less marked for ethyl acetate fraction (D) than for the decoction.
authors.affiliation: CNRS, UMR EcoFoG (AgroParisTech, CIRAD, INRA, UA, UG), Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana. Electronic address: emeline.houel@ecofog.gf.
authors.forename: Emeline
authors.initials: E
authors.lastname: Houël
authors.affiliation: Laboratoire d'Innovation Thérapeutique UMR CNRS 7200, LabEx Medalis, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch cedex, France; Institut de Parasitologie et de Pathologie Tropicale de Strasbourg (IPPTS) - Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Nardella
authors.affiliation: UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Jullian
authors.affiliation: UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Laboratoire d'Innovation Thérapeutique UMR CNRS 7200, LabEx Medalis, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vonthron-Sénécheau
authors.affiliation: Plate-forme de Chimie Biologique Intégrative de Strasbourg UMS 3286 CNRS-Université de Strasbourg, LabEx Medalis et FMTS, ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Villa
authors.affiliation: Plate-forme de Chimie Biologique Intégrative de Strasbourg UMS 3286 CNRS-Université de Strasbourg, LabEx Medalis et FMTS, ESBS Pôle API, Bld Sébastien Brant, 67412 Illkirch Cedex, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Obrecht
authors.affiliation: Swiss Tropical and Public Health Institution, Socinstrasse 57, 4002 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana.
authors.forename: Eliane
authors.initials: E
authors.lastname: Bourreau
authors.affiliation: Laboratoire Ecologie,évolution, interactions des systèmes amazoniens (LEEISA), CNRS, Université de Guyane, IFREMER, 97300 Cayenne, French Guiana.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Odonne
authors.affiliation: Museum National d'Histoire Naturelle, UMR 208 PALoc, MNHN-IRD, BP 165, 97323 Cayenne cedex, French Guiana.
authors.forename: Marie
authors.initials: M
authors.lastname: Fleury
authors.affiliation: UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bourdy
authors.affiliation: CNRS - Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Eparvier
authors.affiliation: UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deharo
authors.affiliation: CNRS - Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France; Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire Océanologique, 66650 Banyuls/Mer, France. Electronic address: didier.stien@cnrs.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Stien
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005616:French Guiana; D005638:Fruit; D006801:Humans; D007199:Indians, South American; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D018547:Plant Stems; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D031647:Psidium; D000067996:RAW 264.7 Cells; D051381:Rats; D014709:Vero Cells
chemical_list: D000893:Anti-Inflammatory Agents; D000962:Antimalarials; D016207:Cytokines; D005419:Flavonoids; D010936:Plant Extracts; C519462:guaijaverin; D009569:Nitric Oxide
keywords: Antimalarial; Cytokines; French guiana; Glycosylated flavonols; Psidium acutangulum; Traditional remedy