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

Ethnopharmacological relevance: Leaves and rhizomes of Renealmia thyrsoidea (Ruiz and Pay.) Poepp. and Endi. 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 PPAR1 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 (MU), 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 (16), one dihydrobenzofuranone (7) and four fnlavonoids (811) were isolated from the leaves. Alongside, two ulavonoids (1213) and five diarylheptanoids (1418) 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 1418 were also screened for their ability to activate PPAR1 nuclear receptor in macwphages. compounds 17 and 18 bearing a Michael acceptor moiety strongly increased the expression of PPAR1 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 PPAR1 activators from the rhizomes. These results are in agreement with the traditional uses of the different parts of Renealmia thy rsoidea.