In Vitro and In Vivo Evaluation of Essential Oil from Artemisia absinthium L. Formulated in Nanocochleates against Cutaneous Leishmaniasis

Abstract

Background: Leishmaniasis is a zoonotic disease caused by protozoan parasites from Leishmania genus. Currently, there are no effective vaccines available and the available therapies are far from ideal. In particular, the development of new therapeutic strategies to reduce the infection caused by Leishmania amazonensis could be considered desirable. Different plant-derived products have demonstrated antileishmanial activity, including the essential oil (EO) from Artemisia absinthium L. (EO-Aa), Asteraceae. Methods: In the present study, the EO-Aa formulated in nanocochleates (EO-Aa-NC) was investigated in vitro against intracellular amastigotes of L. amazonensis and non-infected macrophages from BALB/c mice. In addition, the EO-Aa-NC was also evaluated in vivo against on experimental cutaneous leishmaniasis, which body weight, lesion progression, and parasite load were determined. Results: EO-Aa-NC displayed IC50 values of 21.5 ± 2.5 μg/mL and 27.7 ± 5.6 μg/mL against intracellular amastigotes of L. amazonensis and non-infected peritoneal macrophage, respectively. In the animal model, the EO-Aa-NC (30 mg/kg/intralesional route/every 4 days 4 times) showed no deaths or weight loss greater than 10%. In parallel, the EO-Aa-NC suppressed the infection in the murine model by approximately 50%, which was statistically superior (p < 0.05) than controls and mice treated with EO-Aa. In comparison with Glucantime®, EO-Aa-NC inhibited the progression of infection as efficiently (p > 0.05) as administration of the reference drug. Conclusions: Encochleation of EO-Aa resulted in a stable, tolerable, and efficacious antileishmanial formulation, facilitating systemic delivery of EO, with increased activity compared to administration of the free EO-Aa. This new formulation shows promising potential to future studies aimed at a new therapeutic strategy to treat leishmaniasis.

Asteraceae Plants as Sources of Compounds Against Leishmaniasis and Chagas Disease

“…Although the formulation exhibited lower efficacy against the amastigote form of L. amazonensis , the animals that received 4 administrations with this nanoformulation (30 mg/kg by intralesional route) for 4 days exhibited smaller lesion size than the untreated mice or those treated with EO itself. The results were similar to those obtained with Glucantime® treatment (Tamargo et al, 2017).…”

In vitro evaluation of anticaries, antimycobacterial, antileishmanial and cytotoxic activities of essential oils from Eremanthus erythropappus and of α-bisabolol, their major sesquiterpene

“…Previous studies of antiparasitic activities have established that EOs can be highly active (IC 50 < 10 μg/mL), active (IC 50 > 10 < 50 μg/mL), moderately active (IC 50 > 50 < 100 μg/mL) or inactive (IC 50 > 100 μg/mL) (Estevam et al, 2017). Not only EL-EO and ES-EO exhibit strong leishmanicidal activity, but also other species of the family Asteraceae stand out as producers of active EOs against parasites of the genus Leishmania: Artemisia campestris (Aloui et al, 2016), Artemisia herba-alba (Tamargo et al, 2017), Artemisia absinthium (Tamargo et al, 2017), Artemisia abyssinica (Tariku et al, 2010), Vernonia brasiliana (Martins et al, 2015b) and Vernonia polyanthes (Moreira et al, 2017). Leishmanicidal activity exhibited by EOs from E. erythropappus can be explained by the high concentration of α-bisabolol, which had also been previously identified in EOs from Vanillosmopis arborea.…”

Bixa orellana L. (Bixaceae) and Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) Essential Oils Formulated in Nanocochleates against Leishmania amazonensis

“…Nevertheless, some studies have been found in scientific literature, including: (i) the oral administration of AmB-loaded cochleates in L. donovani infected mice [28,29], (ii) the encochleation of AmB against L. chagasi [30] and (iii) the proteoliposome-derived cochleates in a model of CL by L. major [31]. Recently, our research group evaluated the antileishmanial activity of the EO from Artemisia absinthium L. presented in a stable, tolerable and efficacious nanocochleate formulation [32].…”

“…The dehydration–hydration modified method was employed to prepare nanocochleates (NC) containing EO-Bo or EO-Da, as previously described [32]. A suspension of opalescence aspect was obtained, in correspondence with the formation of small spherical vesicles like liposomes.…”