Monoterpenic aldehydes as potential anti-Leishmania agents: activity of Cymbopogon citratus and citral on L. infantum, L. tropica and L. major.
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 IC(50) concentrations ranging from 25 to 52 μg/ml and from 34 to 42 μg/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.
Faculdade de Farmácia/CEF, Universidade de Coimbra, Azinhaga de Santa Comba, 3030-548 Coimbra, Portugal.
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D000080462:Acyclic Monoterpenes; D000447:Aldehydes / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000633:toxicity; D002417:Cattle; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D031743:Cymbopogon / Q000737:chemistry*; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000648:ultrastructure; D018314:Leishmania infantum / Q000187:drug effects; D018320:Leishmania major / Q000187:drug effects; D007895:Leishmania tropica / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D039821:Monoterpenes / Q000494:pharmacology* / Q000633:toxicity; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010718:Phosphatidylserines / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000080462:Acyclic Monoterpenes; D000447:Aldehydes; D000981:Antiprotozoal Agents; D039821:Monoterpenes; D009822:Oils, Volatile; D010718:Phosphatidylserines; D010936:Plant Extracts; C007076:citral