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Leishmanicidal activity of α-bisabolol from Tunisian chamomile essential oil

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Abstract

According to the World Health Organization, leishmaniasis is considered as a major neglected tropical disease causing an enormous impact on global public health. Available treatments were complicated due to the high resistance, toxicity, and high cost. Therefore, the search for novel sources of anti-leishmania agents is an urgent need. In the present study, an in vitro evaluation of the leishmanicidal activity of the essential oil of Tunisian chamomile (Matricaria recutita L.) was carried out. Chamomile essential oil exhibits a good activity on promastigotes forms of L. amazonensis and L. infantum with a low inhibitory concentration at 50% (IC50) (10.8 ± 1.4 and 10.4 ± 0.6 μg/mL, respectively). Bio-guided fractionation was developed and led to the identification of (−)-α-bisabolol as the most active molecule with low IC50 (16.0 ± 1.2 and 9.5 ± 0.1 μg/mL for L. amazonensis and L. infantum, respectively). This isolated sesquiterpene alcohol was studied for its activity on amastigotes forms (IC50 = 5.9 ± 1.2 and 4.8 ± 1.3 μg/mL, respectively) and its cytotoxicity (selectivity indexes (SI) were 5.4 and 6.6, respectively). The obtained results showed that (−)-α-bisabolol was able to activate a programmed cell death process in the promastigote stage of the parasite. It causes phosphatidylserine externalization and membrane damage. Moreover, it decreases the mitochondrial membrane potential and total ATP levels. These results highlight the potential use of (−)-α-bisabolol against both L. amazonensis and L. infantum, and further studies should be undertaken to establish it as novel leishmanicidal therapeutic agents.

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Funding

This work was supported by the grants RICET (project no. RD12/0018/0012 of the program of Redes Temáticas de Investigación Cooperativa, FIS), Spanish Ministry of Health, Madrid, Spain, the Project PI13/00490 “Protozoosis Emergentes por Amebas de Vida Libre: Aislamiento, Caracterización, Nuevas Aproximaciones Terapéuticas y Traslación Clínica de los Resultados” from the Instituto de Salud Carlos III, and Project ref. AGUA3 “Amebas de Vida Libre como Marcadores de Calidad del Agua” from CajaCanarias Fundación. SH was supported by the “Laboratoire d’Epidémiologie d’Infections Enzootiques des Herbivores en Tunisie” (Ministère de l’enseignement supérieur, Tunisia) and by the “Ayudas para estancias de estudiantes de posgrado e investigadores americanos y africanos—2016” of the University of La Laguna. JLM was supported by the Ramón y Cajal Subprogramme from the Spanish Ministry of Economy and Competitivity RYC-2011-08863. ILB and IAJ were supported by the SAF2015-65113-C2-1-R MINECO, Spain Project and by FEDER funds from the EU. IS and ALA were supported by the Agustin de Bethancourt Programme.

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Hajaji, S., Sifaoui, I., López-Arencibia, A. et al. Leishmanicidal activity of α-bisabolol from Tunisian chamomile essential oil. Parasitol Res 117, 2855–2867 (2018). https://doi.org/10.1007/s00436-018-5975-7

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