Trypanocidal and Leishmanicidal Activities of Flavonoids from Argentine Medicinal Plants

Abstract

In vitro trypanocidal and leishmanicidal activities of the flavonoids hispidulin, from Ambrosia tenuifolia, and santin, from Eupatorium buniifolium, are reported. A sensitive technique that takes advantage of ((3)H)thymidine uptake by dividing trypanosomatids has been adjusted for quantification of the parasiticidal effect of the natural products. The IC(50) values for hispidulin and santin on Trypanosoma cruzi epimastigotes were 46.7 and 47.4 muM, respectively. On trypomastigotes, the IC(50) values were 62.3 microM for hispidulin and 42.1 microM for santin. Hispidulin was more active than santin on promastigotes of Leishmania mexicana (IC(50) = 6.0 microM versus 32.5 microM). No cytotoxic activity was observed on lymphoid cells, making hispidulin and santin potential lead compounds for the development of new natural drugs. This is the first report on the trypanocidal and leishmanicidal activities of these flavonoids and on the presence of santin in E. buniifolium.

Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae)

“…The aerial parts of A. tenuifolia (1,000 g) were air dried, ground to powder, and extracted with dichloromethanemethanol (1:1). This organic extract was fractionated into five fractions (F 1AT to F 5AT ) as previously described (30). Pure compound 1 was obtained from fraction F 4AT as colorless crystals.…”

“…Growth inhibition of T. cruzi epimastigotes was evaluated by a [ 3 H]thymidine uptake assay for fractions F 1AT to F 5AT and compounds 1 and 2, as previously described (30). Parasites were adjusted to a cell density of 1.5 ϫ 10 6 /ml and cultured in the presence of 0.01 to 100 g/ml of each fraction or pure compound for 72 or 120 h. Benznidazole (5 to 20 M; Roche) was used as positive control.…”

“…Parasites were seeded (150 l/well) in duplicate in a 96-well microplate, and 2 l of each compound/well (1 to 100 g/ml, final concentration) or control was added. Plates were incubated for 24 h, and the remaining live parasites were counted in a Neubauer chamber as previously described (30 Cytotoxicity assay. T-lymphocyte suspensions from BALB/c mice (weighing 22 Ϯ 2 g) were employed for the determination of cell viability by the trypan blue dye exclusion method in the absence and presence of increasing concentrations of the pure compounds (0.1, 1, 10, and 50 g/ml) during 3 or 24 h, as previously described (1,30).…”

“…Among them, the organic extract of Ambrosia tenuifolia showed trypanocidal activity with 81.1 Ϯ 0.8% (mean Ϯ standard error of the mean [SEM]) growth inhibition of parasites when used at 100 g/ml (29). Biossay-guided fractionation of this extract led to the isolation and identification of the flavonoid hispidulin, which has significant trypanocidal and leishmanicidal activities (30). The present investigation was undertaken in order to isolate and identify other bioactive compounds that may account for the trypanocidal activity of this species.…”

Evaluation of antitrypanosomal and anti inflammatory activities of selected Nigerian medicinal plants in mice

“…Natural products (plants and animals) are important sources of new drugs because their derivatives are extremely useful as lead structures for synthetic modification and optimization of bioactivity (Sülsen et al, 2007). In furtherance of the efforts on sourcing for novel molecules from natural sources in combating African animal trypanosomosis, previous research on in vivo antitrypanosomal activity is very limited compared to the in vitro experiments, and in the few in vivo studies found in literature, no complete cure without relapses was recorded for plants such as Alstonia boonei bark, Annona senegalensis root, Morinda lucida leaves and Picralima nitida (Wosu and Ibe, 1989).…”