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Essential oils (EO) extracted from fruits, spices and aromatic herbs are recognized for their diverse pharmacological properties, including antiprotozoal activity. Tegumentary leishmaniasis is a challenging infectious disease due to the lack of approved vaccines and the high toxicity of the available treatments. In this study, we determined the chemical profile of 14 essential oils by gas chromatography-mass spectrometry (GC-MS). The cytotoxicity and anti-Leishmania amazonensis activities were determined by colorimetric assays based on tetrazolium salt and resazurin reductions. In addition, alterations in parasite mitochondrial membrane potential and reactive oxygen species production were investigated as possible mechanisms of action. Among the samples, Piper callosum (PCEO) and Zingiber officinale (ZOEO) oils stood out by showing the best activity against axenic amastigotes with 50% inhibitory concentration (IC50) of 21 ±1.5 and 19 ±3.5 µg/ml, respectively. Moreover, PCEO and ZOEO presented low cytotoxic potential against mice peritoneal macrophages with selectivity indexes of 17 and 9.5, respectively. Piper aduncum (PAEO) oil, PCEO, and ZOEO showed no hemolytic activity (> 2 mg/ml). In addition, PCEO showed no cytotoxicity against the VERO cell line. Amastigotes treated with PCEO exhibited mitochondrial membrane depolarization and elevated intracellular ROS levels. The sesquiterpenes safrole and zingiberene were the main components of PCEO and ZOEO, respectively. These results highlight the potential of essential oils to combat tegumentary leishmaniasis.
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