Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer’s, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.

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.

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Current antileishmanial drugs are toxic, expensive, and resistance to them has emerged. Several studies have focused on natural products as alternatives. In the present work, the chemical composition, in vitro antileishmanial activity, cytotoxicity effects, and the influence on mitochondrial function of the essential oil from Tagetes lucida Cav. was determined, as well its main compound estragole. Forty-nine compounds were detected in the oil by gas chromatography-mass spectrometry (GC-MS), of which estragole was the main constituent (97%). The oil showed inhibition of the promastigotes of L. tarentolae and L. amazonensis (IC50 = 61.4 and 118.8 µg/mL, respectively), decreased oxygen consumption of L. tarentolae, disrupted mitochondrial membrane potential in L. amazonensis, inhibitory activity on the intracellular amastigote of L. amazonensis (IC50 = 14.2 ± 1.6 µg/mL), and cytotoxicity values ranging from 80.8 to 156 µg/mL against murine macrophages and J774 cells. Estragole displayed higher activity on promastigotes (IC50 = 28.5 and 25.5 µg/mL, respectively), amastigotes (IC50 = 1.4 ± 0.1 µg/mL), and cytotoxicity values ranging from 20.6 to 14.5 µg/mL, respectively, while on mitochondria, it caused a decrease of the membrane potential but did not inhibit oxygen consumption. The potential antileishmanial activity of the essential oil from T. lucida and estragole makes these compounds favorable candidates for exploration in further studies.

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Leishmaniasis is a group of neglected tropical diseases caused by protozoan parasites of the Leishmania genus. The absence of effective vaccines and the limitations of current treatments make the search for effective therapies a real need. Different plant-derived essential oils (EOs) have shown antileishmanial effects, in particular from Bixa orellana L. (EO-Bo) and Dysphania ambrosioides (L.) Mosyakin & Clemants (EO-Da). In the present study, the EO-Bo and EO-Da, formulated in nanocochleates (EO-Bo-NC and EO-Da-NC, respectively), were evaluated in vitro and in vivo against L. amazonensis. The EO-Bo-NC and EO-Da-NC did not increase the in vitro inhibitory activity of the EOs, although the EO-Bo-NC showed reduced cytotoxic effects. In the animal model, both formulations (30 mg/kg/intralesional route/every 4 days/4 times) showed no deaths or weight loss greater than 10%. In the animal (mouse) model, EO-Bo-NC contributed to the control of infection (p < 0.05) in comparison with EO-Bo treatment, while the mice treated with EO-Da-NC exhibited larger lesions (p < 0.05) compared to those treated with EO-Da. The enhanced in vivo activity observed for EO-Bo-NC suggests that lipid-based nanoformulations like nanocochleates should be explored for their potential in the proper delivery of drugs, and in particular, the delivery of hydrophobic materials for effective cutaneous leishmaniasis treatment.

The prediction of the antagonistic activity on the receivers of the Angiotensin II (AII) for diverse compounds, using molecular describers of topologic order calculated with the software DRAGON, allowed generate 81 independent variables. A total of 202 compounds divided in two series was used: one of training that included 176 compounds, with 41 compounds in the active group and 135 in the inactive one; and a second serie of prediction, integrated by 26 compounds, of which 7 are considered active and 19 take part in the inactive one. After the carry out of the model's validation, were achieved a 97.73% of good classification for the training serie and a 96.15% of good total classification for the prediction one. The later evaluation in the developed pattern of structures with new molecular entities, that were obtained by molecular modification, showed that 4 of them could be potentially active. The results demonstrated that the factor to modify is the alone since lipophilic property is allowed practically to subtract carbons in the chain carbon atoms and to maintain the activity, not happening this if they modify the heterocyclic systems, what seems to indicate that the same ones are part of the pharmacophore. Comparison settled down with other reported models, using different calculation ways, demonstrated the superiority of the methodology developed in our work. For the development of new drugs, the discovery of new series heads to considered like possible active agents that blockade the receiving AT1 of the angiotensin II is a promissory alternative that opens up to the generation of new libraries of compounds that facilitate the virtual sifted.

Aqueous solubility is an important factor that influence the biological processes where participate ionized molecules like drugs. The experimental