title: Antiplasmodial and anti-inflammatory effects of an antimalarial remedy from the Wayana Amerindians, French Guiana: takamalaimë (Psidium acutangulum Mart. ex DC., Myrtaceae).
abstract: BACKGROUND
  Field investigations highlighted the use of Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh), a small tree used by the Wayana Amerindians in Twenke-Taluhwen and Antecume-Pata, French Guiana, for the treatment of malaria, and administered either orally in the form of a decoction or applied externally over the whole body. This use appears limited to the Wayana cultural group in French Guiana and has never been reported anywhere else. Our goal was to evaluate the antimalarial and anti-inflammatory activities of a P. acutangulum decoction to explain the good reputation of this remedy.
  
  
  METHODS
  Interviews with the Wayana inhabitants of Twenke-Taluhwen and Antecume-Pata were conducted within the TRAMAZ project according to the TRAMIL methodology, which is based on a quantitative and qualitative analysis of medicinal plant uses. A decoction of dried aerial parts of P. acutangulum was prepared in consistency with the Wayana recipe. In vitro antiplasmodial assays were performed on chloroquine-resistant FcB1 ([(3)H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains and on chloroquine sensitive NF54 ([(3)H]-hypoxanthine bioassay) P. falciparum strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) was evaluated on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the decoction was measured on L6 mammalian cells, PBMCs, and RAW cells. A preliminary evaluation of the in vivo antimalarial activity of the decoction, administered orally twice daily, was assessed by the classical four-day suppressive test against P. berghei NK65 in mice.
  
  
  RESULTS
  The decoction displayed a good antiplasmodial activity in vitro against the three tested strains, regardless to the bioassay used, with IC50 values of 3.3µg/mL and 10.3µg/mL against P. falciparum FcB1 and NF54, respectively and 19.0µg/mL against P. falciparum 7G8. It also exhibited significant anti-inflammatory activity in vitro in a dose dependent manner. At a concentration of 50µg/mL, the decoction inhibited the secretion of the following pro-inflammatory cytokines: TNFα (-18%), IL-1β (-58%), IL-6 (-32%), IL-8 (-21%). It also exhibited a mild NO secretion inhibition (-13%) at the same concentration. The decoction was non-cytotoxic against L6 cells (IC50>100µg/mL), RAW cells and PBMC. In vivo, 150µL of the decoction given orally twice a day (equivalent to 350mg/kg/day of dried extract) inhibited 39.7% average parasite growth, with more than 50% of inhibition in three mice over five. The absence of response for the two remaining mice, however, induced a strong standard deviation.
  
  
  CONCLUSIONS
  This study highlighted the in vitro antiplasmodial activity of the decoction of P. acutangulum aerial parts, used by Wayana Amerindians from the Upper-Maroni in French Guiana in case of malaria. Its antioxidant and anti-inflammatory potential, which may help to explain its use against this disease, was demonstrated using models of artificially stimulated cells.
authors: CNRS - UMR Ecologie des Forêts de Guyane (EcoFoG), Institut Pasteur de la Guyane, 23 Avenue Pasteur, BP6010, 97306 Cayenne Cedex, French Guiana. Electronic address: emeline.houel@ecofog.gf.
authors: Emeline
authors: E
authors: Houël
authors: Museum National d'Histoire Naturelle, UMR 208 PALoc, MNHN-IRD, BP 165, 97323 Cayenne Cedex, French Guiana.
authors: Marie
authors: M
authors: Fleury
authors: CNRS-Guyane - USR 3456, 2 avenue Gustave Charlery, 97300 Cayenne, French Guiana.
authors: Guillaume
authors: G
authors: Odonne
authors: 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: Flore
authors: F
authors: Nardella
authors: Université de Toulouse, UMR 152 PharmaDEV, Faculté de Pharmacie, 35 Chemin des Maraîchers, 31062 Toulouse Cedex 9, France; Institut de Recherche pour le Développement (IRD), UMR 152 PharmaDEV, Faculté de Pharmacie, 35 Chemin des Maraîchers, 31062 Toulouse Cedex 9, France.
authors: Geneviève
authors: G
authors: Bourdy
authors: Laboratoire d'Innovation Thérapeutique UMR CNRS 7200, LabEx Medalis, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors: Catherine
authors: C
authors: Vonthron-Sénécheau
authors: 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: Pascal
authors: P
authors: Villa
authors: 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: Adeline
authors: A
authors: Obrecht
authors: CNRS - Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors: Véronique
authors: V
authors: Eparvier
authors: Université de Toulouse, UMR 152 PharmaDEV, Faculté de Pharmacie, 35 Chemin des Maraîchers, 31062 Toulouse Cedex 9, France; Institut de Recherche pour le Développement (IRD), UMR 152 PharmaDEV, Faculté de Pharmacie, 35 Chemin des Maraîchers, 31062 Toulouse Cedex 9, France.
authors: Eric
authors: E
authors: Deharo
authors: 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-sur-mer, France. Electronic address: didier.stien@cnrs.fr.
authors: Didier
authors: D
authors: Stien
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D020834:Ethnopharmacology / Q000379:methods; D005616:French Guiana; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D027822:Myrtaceae / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*; D031647:Psidium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000962:Antimalarials; D000981:Antiprotozoal Agents; D007378:Interleukins; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002738:Chloroquine
keywords: Antimalarial; Cytokines; French Guiana; Plasmodium; Psidium acutangulum; Traditional medicine