Leishmanicidal compounds and potent PPAR gamma activators from Renealmia thyrsoidea (Ruiz & Pav.) Poepp. & Endl

2014

Article référencé dans le Web of Science WOS:000347022700018

Cabanillas B. J., Le Lamer A. C., Olagnier D., Castillo D., Arevalo J., Valadeau C., Coste A., Pipy B., Bourdy Geneviève, Sauvain Michel, Fabre Nicolas

Journal of Ethnopharmacology, 2014, 157, p. 149-155 ISSN 0378-8741

Ethnopharmacological relevance: 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 PPAR gamma 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 (MIT), 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 PPAR gamma nuclear receptor in macrophages. Compounds 17 and 18 bearing a Michael acceptor moiety strongly increased the expression of PPAR gamma 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 PPAR gamma activators from the rhizomes. These results are in agreement with the traditional uses of the different parts of Renealmia thyrsoidea.

Entomologie médicale / Parasitologie / Virologie [052] ; Sciences du monde végétal [076]

PEROU

Fonds IRD [F B010063649]

fdi:010063649