Linalool, a Piper aduncum essential oil component, has selective activity against Trypanosoma cruzi trypomastigote forms at 4°C.
BACKGROUND
Recent studies showed that essential oils from different pepper species (Piper spp.) have promising leishmanicidal and trypanocidal activities.


OBJECTIVE
In search for natural compounds against Trypanosoma cruzi, different forms of the parasite were incubated for 24 h at 28ºC or 4ºC with Piper aduncum essential oil (PaEO) or its main constituents linalool and nerolidol.


METHODS
PaEO chemical composition was obtained by GC-MS. Drug activity assays were based on cell counting, MTT data or infection index values. The effect of PaEO on the T. cruzi cell cycle and mitochondrial membrane potential was evaluated by flow cytometry.


RESULTS
PaEO was effective against cell-derived (IC50/24 h: 2.8 μg/mL) and metacyclic (IC50/24 h: 12.1 μg/mL) trypomastigotes, as well as intracellular amastigotes (IC50/24 h: 9 μg/mL). At 4ºC - the temperature of red blood cells (RBCs) storage in blood banks - cell-derived trypomastigotes were more sensitive to PaEO (IC50/24 h = 3.8 μg/mL) than to gentian violet (IC50/24 h = 24.7 mg/mL). Cytotoxicity assays using Vero cells (37ºC) and RBCs (4ºC) showed that PaEO has increased selectivity for cell-derived trypomastigotes. Flow cytometry analysis showed that PaEO does not affect the cell cycle of T. cruzi epimastigotes, but decreases their mitochondrial membrane potential. GC-MS data identified nerolidol and linalool as major components of PaEO, and linalool had trypanocidal effect (IC50/24 h: 306 ng/mL) at 4ºC.


CONCLUSIONS
The trypanocidal effect of PaEO is likely due to the presence of linalool, which may represent an interesting candidate for use in the treatment of potentially contaminated RBCs bags at low temperature.
Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Biologia Celular, Curitiba, PR, Brasil.
Luz Helena
LH
Villamizar
Universidade Federal de Lavras, Departamento de Química, Lavras, MG, Brasil.
Maria das Graças
MD
Cardoso
Universidade Federal de Lavras, Departamento de Química, Lavras, MG, Brasil.
Juliana de
J
Andrade
Universidade Federal de Lavras, Departamento de Química, Lavras, MG, Brasil.
Maria Luisa
ML
Teixeira
Fundação Oswaldo Cruz-Fiocruz, Instituto Carlos Chagas, Laboratório de Biologia Celular, Curitiba, PR, Brasil.
Maurilio José
MJ
Soares
D000080462:Acyclic Monoterpenes; D000818:Animals; D001681:Biological Assay; D002522:Chlorocebus aethiops; D003080:Cold Temperature; D008401:Gas Chromatography-Mass Spectrometry; D020128:Inhibitory Concentration 50; D039821:Monoterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D009822:Oils, Volatile / Q000494:pharmacology*; D031701:Piper / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D009822:Oils, Volatile; D014344:Trypanocidal Agents; C018584:linalool