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

[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 pr...

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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
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Summary:[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.
ISSN:0014-4894
1090-2449
DOI:10.1016/j.exppara.2011.12.012