Monoterpenic aldehydes as potential anti-Leishmania agents: Activity of Cymbopogon citratus and citral on L. infantum, L. tropica and L. major

• Published in: Experimental parasitology 2012-03, Vol.130 (3), p.223-231
• Main Authors: Machado, M., Pires, P., Dinis, A.M., Santos-Rosa, M., Alves, V., Salgueiro, L., Cavaleiro, C., Sousa, M.C.
• Format: Article
• Language: English
• Subjects: Aldehydes - pharmacology; Aldehydes - toxicity; Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Antiprotozoals; apoptosis; Cattle; cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line; chromatin; citral; Cymbopogon - chemistry; Cymbopogon citratus; Drug action; Drug development; Essential oil; essential oils; Flow Cytometry; In vitro activity; Infectious diseases (ID); Inhibitory Concentration 50; Leishmania - drug effects; Leishmania - ultrastructure; Leishmania infantum; Leishmania infantum - drug effects; Leishmania major; Leishmania major - drug effects; Leishmania tropica; Leishmania tropica - drug effects; Leishmaniainfantum; Leishmaniamajor; leishmaniasis; Leishmaniatropica; Medicinal plants; membrane potential; Membrane Potential, Mitochondrial - drug effects; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; mitochondrial membrane; Monoterpenes - pharmacology; Monoterpenes - toxicity; new drugs; nuclear membrane; Oils, Volatile - chemistry; Oils, Volatile - pharmacology; Oils, Volatile - toxicity; parasitology; phosphatidylserines; Phosphatidylserines - metabolism; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - toxicity; promastigotes; Ultrastructure
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2011.12.012

[Display omitted] ► Cymbopogon citratus essential oil, plant-derived product, was active on Leishmania. ► Anti-Leishmania activity of C. citratus was mainly due to citral compound. ► Essential oil and citral promoted depolarization of mitochondrial membrane. ► C. citratus essential oil and citral promoted cell-cycle arrest at the G(0)/G(1) phase. ► C. citratus and citral represent valuable sources for Leishmania infections control. In order to contribute for the search of new drugs for leishmaniasis, we study the susceptibility of Leishmania infantum, Leishmania tropica and Leishmania major to Cymbopogon citratus essential oil and major compounds, mrycene and citral. C. citratus and citral were the most active inhibiting L. infantum, L. tropica and L. major growth at IC50 concentrations ranging from 25 to 52μg/ml and from 34 to 42μg/ml, respectively. L. infantum promastigotes exposed to essential oil and citral underwent considerable ultrastructural alterations, namely mitochondrial and kinetoplast swelling, autophagosomal structures, disruption of nuclear membrane and nuclear chromatin condensation. C. citratus essential oil and citral promoted the leishmanicidal effect by triggering a programmed cell death. In fact, the leishmanicidal activity was mediated via apoptosis as evidenced by externalization of phosphatidylserine, loss of mitochondrial membrane potential, and cell-cycle arrest at the G(0)/G(1) phase. Taken together, ours findings lead us to propose that citral was responsible for anti-Leishmania activity of the C. citratus and both may represent a valuable source for therapeutic control of leishmaniasis.