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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 163404, 6 pages
http://dx.doi.org/10.1155/2013/163404
Research Article

Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana

1Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, Argentina
2Instituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2°P, 1113 Buenos Aires, Argentina
3Instituto de Investigaciones en Tecnología Química (INTEQUI-CONICET), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina

Received 9 April 2013; Accepted 20 May 2013

Academic Editor: William Setzer

Copyright © 2013 Patricia Barrera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host’s cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism.