title: In vivo anti-Trypanosoma cruzi activity of hydro-ethanolic extract and isolated active principles from Aristeguietia glutinosa and mechanism of action studies.
abstract: The currently available treatments for Chagas disease show limited therapeutic potential and are associated with serious side effects. Attempting to find alternative drugs isolated from Nature as agents against Trypanosoma cruzi has been our goal. Recently, we have demonstrated the in vitro anti-T. cruzi activities of two secondary metabolites isolated from the hydro-ethanolic extract of the aerial parts of Aristeguietia glutinosa (Lam.), (family Asteraceae). These active principles displayed poor hemolytic activity, low toxicity against murine macrophages, and absence of mutagenicity. Herein, proof of concept in vivo studies of the whole hydro-ethanolic extract of the aerial parts of Aristeguietia glutinosa and of the most active component isolated from the hydro-ethanolic extract, i.e., (+)-15-hydroxy-7-labden-17-al, was done in a murine acute model of Chagas disease. Both treatments caused a decrease in the animals' parasitemia. Metabolomic mechanism of action studies were done by 1H-NMR, both on the extract and on the active compounds, examining the effects of the metabolites both on membrane sterol biosynthesis and mitochondrial dehydrogenases, whereby we found that one of the metabolites inhibited the activity of the parasite mitochondrial dehydrogenases and the other inhibited the biosynthesis of parasite membrane sterols. The results are interesting in the context of popular use of plants for the treatment of Chagas disease.
authors: Grupo de Química Medicinal-Laboratorio de Química Orgánica-Facultad de Ciencias-Facultad de Química-UdelaR, Iguá 4225, Montevideo, C.P. 11400, Uruguay. jvarelaubillos@gmail.com.
authors: Javier
authors: J
authors: Varela
authors: Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, 1120, Paraguay. elvsern@hotmail.com.
authors: Elva
authors: E
authors: Serna
authors: Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, 1120, Paraguay. susitorres1@hotmail.com.
authors: Susana
authors: S
authors: Torres
authors: Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, 1120, Paraguay. gloriayaluff@yahoo.com.
authors: Gloria
authors: G
authors: Yaluff
authors: Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, 1120, Paraguay. nverabilbao@gmail.com.
authors: Ninfa I Vera
authors: NI
authors: de Bilbao
authors: Carrera Química Farmacéutica, Facultad de Ciencias Químicas, Universidad Central de Ecuador, Quito, C.P. 170150, Ecuador. patriciomino@yahoo.com.
authors: Patricio
authors: P
authors: Miño
authors: Carrera Química Farmacéutica, Facultad de Ciencias Químicas, Universidad Central de Ecuador, Quito, C.P. 170150, Ecuador. xchiriboga@yahoo.com.
authors: Ximena
authors: X
authors: Chiriboga
authors: Grupo de Química Medicinal-Laboratorio de Química Orgánica-Facultad de Ciencias-Facultad de Química-UdelaR, Iguá 4225, Montevideo, C.P. 11400, Uruguay. hcerecetto@cin.edu.uy.
authors: Hugo
authors: H
authors: Cerecetto
authors: Grupo de Química Medicinal-Laboratorio de Química Orgánica-Facultad de Ciencias-Facultad de Química-UdelaR, Iguá 4225, Montevideo, C.P. 11400, Uruguay. mgonzalezhormaizteguy@gmail.com.
authors: Mercedes
authors: M
authors: González
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D019659:Asteraceae / Q000378:metabolism*; D014355:Chagas Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000737:chemistry; D005260:Female; D005650:Fumarates / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D013261:Sterols / Q000096:biosynthesis; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D019802:Succinic Acid / Q000378:metabolism; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: C000596943:15-hydroxy-7-labden-17-al; D000981:Antiprotozoal Agents; D004224:Diterpenes; D005650:Fumarates; D010936:Plant Extracts; D013261:Sterols; D014344:Trypanocidal Agents; D000431:Ethanol; D019802:Succinic Acid; D008291:Malate Dehydrogenase; D013385:Succinate Dehydrogenase