Abstract
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.
Highlights
Leishmania species is the causative agent of leishmaniasis
Given the ineffectiveness of the current therapeutic approaches, the appearance of drug-resistant microorganisms, the rate of incidence of parasitic diseases, linked with the associated toxicity, bioavailability, and care costs, more intense studies are needed towards effective drugs discovery [4]
The essential oil from the L. luisieri and L. viridis aerial parts was isolated by water distillation for 3 h from air dried material, using a Clevenger-type apparatus, following the procedure described in the European Pharmacopoeia (Council of Europe, 1997)
Summary
Leishmania species is the causative agent of leishmaniasis. This unicellular trypanosomatid induces a broad-spectrum disease, varying from localized, self-healing, and cutaneous lesions to disfiguring forms of mucocutaneous leishmaniasis, possibly even lethal visceral forms, when neglected [1,2,3].Chemotherapy treatment is considered the most cost-effective intervention on parasitic diseases.given the ineffectiveness of the current therapeutic approaches, the appearance of drug-resistant microorganisms, the rate of incidence of parasitic diseases, linked with the associated toxicity, bioavailability, and care costs, more intense studies are needed towards effective drugs discovery [4].Plant extracts, characterized by their rich diversity and complexity of secondary metabolites, involved on the expression of evolutionary strategies to overcome competitive disadvantages of plants, comprise valuable collections of compounds to screen bioactive effects [5,6]. Given the ineffectiveness of the current therapeutic approaches, the appearance of drug-resistant microorganisms, the rate of incidence of parasitic diseases, linked with the associated toxicity, bioavailability, and care costs, more intense studies are needed towards effective drugs discovery [4]. EO composes a pool of hydrophobic molecules that diffuse across cell membranes [7] and, gain advantage and interact with intracellular targets [8]. They can be conceived as a promisor approach on parasite infections control and even treatment. Despite beings highly cost-effective, have been increasingly associated with the appearance of drug-resistant microorganisms. Cell viability effects were estimated by using the tetrazolium-dye (MTT)
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