In vitro and in vivo trypanocidal activity of flavonoids from Delphinium staphisagria against Chagas disease.


Marín, C; Ramírez-Macías, I; López-Céspedes, A; Olmo, F; Villegas, N; Díaz, JG; Rosales, MJ; Gutiérrez-Sánchez, R; Sánchez-Moreno, M; (2011) In vitro and in vivo trypanocidal activity of flavonoids from Delphinium staphisagria against Chagas disease. Journal of natural products, 74 (4). pp. 744-50. ISSN 0163-3864 DOI: https://doi.org/10.1021/np1008043

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Abstract

The in vitro and in vivo trypanocidal activities of nine flavonoids (1-9) isolated from the aerial parts of Delphinium staphisagria have been studied in both the acute and chronic phases of Chagas disease. The antiproliferative activity of these substances against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) in some cases exhibited more potent antitrypanosomatid activity and lower toxicity than the reference drug, benznidazole. Studies in vitro using ultrastructural analysis together with metabolism-excretion studies were also performed in order to identify the possible action mechanism of the compounds tested. Alterations mainly at the level of the mitochondria may explain metabolic changes in succinate and acetate production, perhaps due to the disturbance of the enzymes involved in sugar metabolism within the mitochondrion. In vivo studies provided results consistent with those observed in vitro. No signs of toxicity were detected in mice treated with the flavonoids tested, and the parasitic charge was significantly lower than in the control assay with benznidazole. The effects of these compounds were also demonstrated with the change in the anti-T. cruzi antibody levels during the chronic stage.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Neglected Tropical Diseases Network
PubMed ID: 21466157
Web of Science ID: 289742300032
URI: http://researchonline.lshtm.ac.uk/id/eprint/2913282

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