Lavandula Luisieri and Lavandula Viridis Essential Oils as Upcoming Anti-Protozoal Agents: A Key Focus on Leishmaniasis
Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
Centro de Investigação em Biodiversidade e Recursos Genéticos (CIBIO-UP), Universidade do Porto, 4485-661 Vairão, Portugal
Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
Institute for Research and Innovation in Health (I3S), University of Porto, 4200-135 Porto, Portugal
Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
Chemical Process Engineering and Forest Products Research Center, University of Coimbra, 3030-790 Coimbra, Portugal
Center for Neurosciences and Cell Biology (CNC), University of Coimbra, 3030-790 Coimbra, Portugal
Author to whom correspondence should be addressed.
Appl. Sci. 2019, 9(15), 3056; https://doi.org/10.3390/app9153056
Received: 5 June 2019 / Revised: 11 July 2019 / Accepted: 12 July 2019 / Published: 29 July 2019
(This article belongs to the Special Issue New bioactive Molecules: Challenges in Environmental and Nutritional Health)
Background and objectives: Leishmania species is the causative agent of leishmaniasis, a broad-spectrum clinical condition that can even be life-threatening when neglected. Current therapeutic strategies, despite beings highly cost-effective, have been increasingly associated with the appearance of drug-resistant microorganisms. Thus, an increasing number of thorough studies are needed towards upcoming drug discovery. This study aims to reveal the anti-protozoa activity of Lavandula luisieri and Lavandula viridis essential oils (EO) and their main components (1,8-cineole, linalool, and borneol). Materials and Methods: L. luisieri and L. viridis EO and their main components’ leishmanicidal effects were tested in vitro against Leishmania infantum, Leishmania major, and Leishmania tropica strains. Cell viability effects were estimated by using the tetrazolium-dye (MTT) colorimetric method, morphological changes were assessed by scanning electron microscopy (SEM) and ultrastructural investigation by transmission electronic microscopy (TEM). Phosphatidylserine externalization, mitochondrial membrane potential (MMP), and cathepsin D activity assessment were also carried out. Finally, cytotoxic activity of the studied matrices was also determined in mammalian cells. Results: Plant-studied EO exhibited prominent anti-Leishmania effects (IC50 = 31–263 µg/mL), with L. luisieri being the most active one. At concentrations corresponding to IC50 values, EO-exposed L. infantum promastigotes suffered marked ultrastructural modifications. The presence of aberrant-shaped cells, mitochondrial and kinetoplast swelling, and autophagosomal structures were the most common evidenced changes. L. luisieri EO exerted its leishmanicidal activity through different mechanisms, but mainly through unleashing apoptosis. Phosphatidylserine externalization, mitochondrial membrane potential loss, and cell-cycle arrest at G(0)/G(1) phase were the most remarkable apoptosis-mediated aspects. Inhibition of cathepsin D activity was also observed. No toxic effects were found on macrophage cells. Conclusions: L. luisieri seems to be an upcoming source of bioactive molecules for leishmaniasis control and to find leading molecules for new drugs formulation against Leishmania infections.