title: In vitro and in vivo trypanocidal activity of flavonoids from Delphinium staphisagria against Chagas disease.
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.
authors.affiliation: Department of Parasitology, University of Granada, Severo Ochoa s/n, E-18071 Granada, Spain.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Marín
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ramírez-Macías
authors.forename: Angeles
authors.initials: A
authors.lastname: López-Céspedes
authors.forename: Francisco
authors.initials: F
authors.lastname: Olmo
authors.forename: Noelia
authors.initials: N
authors.lastname: Villegas
authors.forename: Jesús G
authors.initials: JG
authors.lastname: Díaz
authors.forename: María José
authors.initials: MJ
authors.lastname: Rosales
authors.forename: Ramón
authors.initials: R
authors.lastname: Gutiérrez-Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Moreno
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D002522:Chlorocebus aethiops; D031882:Delphinium / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000097:blood / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
chemical_list: D005419:Flavonoids; D014344:Trypanocidal Agents