Phylobioactive hotspots in plant resources used to treat Chagas disease

Abstract

Summary Globally, more than six million people are infected with Trypanosoma cruzi , the causative protozoan parasite of the vector-borne Chagas disease (CD). We conducted a cross-sectional ethnopharmacological field study in Bolivia among different ethnic groups where CD is hyperendemic. A total of 775 extracts of botanical drugs used in Bolivia in the context of CD and botanical drugs from unrelated indications from the Mediterranean De Materia Medic a compiled by Dioscorides two thousand years ago were profiled in a multidimensional assay uncovering different antichagasic natural product classes. Intriguingly, the phylobioactive anthraquinone hotspot matched the antichagasic activity of Senna chloroclada , the taxon with the strongest ethnomedical consensus for treating CD among the Izoceño-Guaraní. Testing common 9,10-anthracenedione derivatives in T. cruzi cellular infection assays demarcates hydroxyanthraquinone as a potential antichagasic lead scaffold. Our study systematically uncovers in vitro antichagasic phylogenetic hotspots in the plant kingdom as a potential resource for drug discovery based on ethnopharmacological hypotheses.

In Vitro Anti-Trypanosoma cruzi Activity of Halophytes from Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum maritimum L.)

“…No cytotoxicity was detected for falcarindiol up to 100 µM (26 µg/mL), similarly to fraction 1 (CC 50 = 28 µg/mL), while it effectively reduced T. cruzi infection to undetectable levels (maximum activity higher than 100%, like for fraction 1), thus demonstrating that this molecule is highly selective towards T. cruzi amastigotes. In the only studies available on falcarindiol's trypanocidal effects, Salm et al [34] reports that the polyacetylene isolated from Sium sisarum L. had no inhibitory effect on T. cruzi, while Mennai et al [35] describes a low anti-trypanosomal activity of this constituent identified in Pituranthos battandieri Maire. Nevertheless, the former performed antiproliferation assays on T. cruzi epimastigotes (IC 50 > 50 µM) and trypomastigotes (0% parasite release inhibition at 5 µM), and the latter assayed on epimastigote forms of T. cruzi (IC 50 = 121.8 µM).…”

“…The use of different morphological forms of the parasite may explain the divergent reports on the anti-T. cruzi activity of falcarindiol, as compounds can present disparate activity against trypomastigotes, intracellular amastigotes, and epimastigotes [27]. Despite variations in falcarindiol's activity being potentially due to the different life stages of T. cruzi, the concentration could also account for the different results: falcarindiol was only active against epimastigotes at high concentrations (>50 µM) [34,35], and only a low concentration (5 µM) was tested against trypomastigotes in the release assay [34].…”

Travelogues from the Rainforest: Notes on Prof. Otto Sticherʼs 85th birthday

“…Inspired by Ottoʼs molecular pharmacognosy and openness for ethnobotanical studies, and our positive experience in his lab at ETH, Marco Leonti and I continue to carry out ethnopharmacological studies to the present day. I recently went back to the Amazonian forests, this time working on Chagas disease [11,12]. Natural products will never stop inspiring drug development, and pharmacognosy will survive if humanity manages to protect the biogenetic resources.…”

Anti-trypanosomal screening of Salvadoran flora

“…Throughout the history of mankind, natural products have been decisive for the discovery of new drugs, since they have enormous structural diversity as compared to conventional synthetic molecules and the screening of these natural sources remains one of the most attractive routes for this purpose [ 6 , 7 ]. Various plant species have been tested in the search for natural products to combat Chagas disease caused by T. cruzi , exhibiting in many cases high trypanocidal activity and low toxicity [ 8 – 11 ].…”