title: Leishmanicidal compounds and potent PPARγ activators from Renealmia thyrsoidea (Ruiz & Pav.) Poepp. & Endl.
abstract: BACKGROUND
  Leaves and rhizomes of Renealmia thyrsoidea (Ruiz & Pav.) Poepp. & Endl. traditionally used in the Yanesha pharmacopoeia to treat skin infections such as leishmaniasis ulcers, or to reduce fever were chemically investigated to identify leishmanicidal compounds, as well as PPARγ activators.
  
  
  METHODS
  Compounds were isolated through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The viability of Leishmania amazonensis axenic amastigotes was assessed by the reduction of tetrazolium salt (MTT), the cytotoxicity on macrophage was evaluated using trypan blue dye exclusion method, while the percentage of infected macrophages was determined microscopically in the intracellular macrophage-infected assay. The CD36, mannose receptor (MR) and dectin-1 mRNA expression on human monocytes-derived macrophages was evaluated by quantitative real-time PCR.
  
  
  RESULTS
  Six sesquiterpenes (1-6), one dihydrobenzofuranone (7) and four flavonoids (8-11) were isolated from the leaves. Alongside, two flavonoids (12-13) and five diarylheptanoids (14-18) were identified in the rhizomes. Leishmanicidal activity against Leishmania amazonensis axenic amastigotes was evaluated for all compounds. Compounds 6, 7, and 11, isolated from the leaves, showed to be the most active derivatives. Diarylheptanoids 14-18 were also screened for their ability to activate PPARγ nuclear receptor in macrophages. Compounds 17 and 18 bearing a Michael acceptor moiety strongly increased the expression of PPARγ target genes such as CD36, Dectin-1 and mannose receptor (MR), thus revealing interesting immunomodulatory properties.
  
  
  CONCLUSIONS
  Phytochemical investigation of Renealmia thyrsoidea has led to the isolation of leishmanicidal compounds from the leaves and potent PPARγ activators from the rhizomes. These results are in agreement with the traditional uses of the different parts of Renealmia thyrsoidea.
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, Mission IRD Casilla 18-1209, Lima, Peru.
authors.forename: Billy Joel
authors.initials: BJ
authors.lastname: Cabanillas
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France. Electronic address: anne-cecile.le-lamer@univ-tlse3.fr.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Le Lamer
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: David
authors.initials: D
authors.lastname: Olagnier
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Avenida Honorio Delgado 430, San Martin de Porres, Lima, Peru.
authors.forename: Denis
authors.initials: D
authors.lastname: Castillo
authors.affiliation: Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Avenida Honorio Delgado 430, San Martin de Porres, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Arevalo
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, Mission IRD Casilla 18-1209, Lima, Peru.
authors.forename: Céline
authors.initials: C
authors.lastname: Valadeau
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Coste
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, Mission IRD Casilla 18-1209, Lima, Peru.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bourdy
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, Mission IRD Casilla 18-1209, Lima, Peru.
authors.forename: Michel
authors.initials: M
authors.lastname: Sauvain
authors.affiliation: Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fabre
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007894:Leishmania mexicana / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D060888:Real-Time Polymerase Chain Reaction; D027343:Rhizome; D030521:Zingiberaceae / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D047495:PPAR gamma; D010936:Plant Extracts
keywords: Leishmanicidal activity; Medicinal plants; PPARγ; Peru; Renealmia thyrsoidea; Zingiberaceae