Croton cajucara crude extract and isolated terpenes: activity on Trypanosoma cruzi

• Published in: Parasitology research (1987) 2010-10, Vol.107 (5), p.1193-1204
• Main Authors: Campos, Monica C. O, Salomão, Kelly, Castro-Pinto, Denise B, Leon, Leonor L, Barbosa, Helene S, Maciel, Maria Aparecida M, de Castro, Solange L
• Format: Article
• Language: English
• Subjects: Amastigotes; Animals; Antiprotozoal Agents - isolation & purification; Antiprotozoal Agents - pharmacology; Bark; Benznidazole; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Complex Mixtures - isolation & purification; Complex Mixtures - pharmacology; Croton - chemistry; Croton cajucara; Diterpenes, Clerodane - isolation & purification; Diterpenes, Clerodane - pharmacology; Epimastigotes; Fundamental and applied biological sciences. Psychology; General aspects; General aspects and techniques. Study of several systematic groups. Models; Health aspects; Immunology; Infection; Inhibitory Concentration 50; Invertebrates; Macrophages, Peritoneal - parasitology; Medical Microbiology; Medicinal plants; Mice; Microbiology; Mitochondria; Original Paper; Parasitic Sensitivity Tests; Plant Bark - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Stems - chemistry; Plasma membranes; Terpenes; Triterpenes - isolation & purification; Triterpenes - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanothione reductase; Trypomastigotes
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-010-1988-6

Croton cajucara is a plant found in the Amazon region and is known for its medicinal properties. The effects of the methanolic extract of the stem bark of C. cajucara (MCC) and of the isolated terpenes, trans-dehydrocrotonin (t-DCTN) and acetyl aleuritolic acid (AAA), were investigated using four isolates of Trypanosoma cruzi. In assays with trypomastigotes, the extract was more active than the isolated compounds, presenting IC₅₀ in the range of 10 to 50 μg/mL. The trypanocidal effect of MCC, AAA and benznidazole was significantly higher in the GLT291 and C45 strains, which were recently isolated from wild animals. MCC and AAA caused a dose-dependent inhibition of epimastigote proliferation. In assays using intracellular amastigotes, AAA and MCC reduced the percent of infection and the endocytic index after 96 h of treatment, at concentrations that were non-toxic to the host cells. MCC inhibited the trypanothione reductase pathway in both epimastigotes and trypomastigotes of all the subpopulations. The absence of AAA activity on the trypanothione reductase pathway in epimastigotes of Dm28c suggests heterogeneity of the biochemical profile between this clone and the three strains. Epimastigotes and trypomastigotes (GLT291) were treated for 24 h with MCC or AAA, and both induced alterations of the plasma membrane, while AAA-treated epimastigotes also displayed mitochondrial damage.