In Vivo Anti-Trypanosoma cruzi Activity of Hydro-Ethanolic Extract and Isolated Active Principles from Aristeguietia glutinosa and Mechanism of Action Studies

Molecules

Javier Varela³  Elva Serna²  Susana Torres²  Gloria Yaluff²  Ninfa I. Vera de Bilbao²  Patricio Miño¹  Ximena Chiriboga¹  Hugo Cerecetto³ 

[1] Carrera Química Farmacéutica, Facultad de Ciencias Químicas, Universidad Central de Ecuador, Quito, C.P. 170150, Ecuador; E-Mails:;Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, Asunción, 1120, Paraguay; E-Mails:;Grupo de Química Medicinal-Laboratorio de Química Orgánica-Facultad de Ciencias-Facultad de Química—UdelaR, Iguá 4225, Montevideo, C.P. 11400, Uruguay; E-Mail:

关键词: anti-T. cruzi activity;    Aristeguietia glutinosa Lam.;    (+)-15-hydroxy-7-labden-17-al;    labdane diterpenoid;    ¹H-NMR metabolomics;   

DOI  :  10.3390/molecules19068488

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.