Leishmaniasis is a group of infectious-parasitic diseases with high mortality rates, and endemic in many regions of the globe. The currently available drugs present serious problems such as high toxicity, costs, and the emergence of drug resistance. This has stimulated research into new antileishmania drugs based on natural products and their derivatives. β-Ocimene is a monoterpene found naturally in the essential oils of many plant species which presents antileishmanial activity, and which has not yet been evaluated for its potential to inhibit the etiological agent of leishmaniasis. The aim of this work was to evaluate the activity of β-ocimene against Leishmania amazonensis, its cytotoxicity, and potential mechanisms of action. β-Ocimene presented direct activity against the parasite, with excellent growth inhibition of promastigotes (IC50 = 2.78 μM) and axenic amastigotes (EC50 = 1.12 μM) at concentrations non-toxic to RAW 264.7 macrophages (CC50 = 114.5 µM). The effect is related to changes in membrane permeability and resulting abnormalities in the parasitic cell shape. These were, respectively, observed in membrane integrity and atomic force microscopy assays. β-Ocimene was also shown to act indirectly, with greater activity against intra-macrophagic amastigotes (EC50 = 0.89 μM), increasing TNF-α, nitric oxide (NO), and reactive oxygen species (ROS), with lysosomal effects, as well as promoting decreases in IL-10 and IL-6. Against intra-macrophagic amastigote forms the selectivity index was higher than the reference drugs, being 469.52 times more selective than meglumine antimoniate, and 42.88 times more selective than amphotericin B. Our results suggest that β-ocimene possesses promising in vitro antileishmania activity and is a potential candidate for investigation in in vivo assays.
Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for Leishmaniamajor and L. (Viannia) braziliensis. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against L. major and 21 lignans against L. braziliensis, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species Justiciaaequilabris (Nees) Lindau. All of the identified compounds were able to inhibit the growth of L. braziliensis promastigotes, with the most active compound, (159) epipinoresinol-4-O-β-d-glucopyranoside, presenting an IC50 value of 5.39 µM and IC50 value of 36.51 µM for L. major. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis.
Leishmaniasis is a group of infectious diseases transmitted to humans during vector bites and caused by protozoans of the genus Leishmania. Conventional therapies face challenges due to their serious side effects, prompting research into new anti-leishmania agents. In this context, we investigated the effectiveness of morolic acid, a pentacyclic triterpene, on L. amazonensis promastigotes and amastigotes. The present study employed the MTT assay, cytokine analysis using optEIATM kits, an H2DCFDA test, and nitric oxide dosage involving nitrite production and Griess reagent. Morolic acid inhibited promastigote and axenic amastigote growth forms at IC50 values of 1.13 µM and 2.74 µM, respectively. For cytotoxicity to macrophages and VERO cells, morolic acid obtained respective CC50 values of 68.61 µM and 82.94 µM. The compound causes damage to the parasite membrane, leading to cellular leakage. In the infection assay, there was a decrease in parasite load, resulting in a CI50 of 2.56 µM. This effect was associated with immunomodulatory activity, altering macrophage structural and cellular parasite elimination mechanisms. Morolic acid proved to be an effective and selective natural compound, making it a strong candidate for future in vivo studies in cutaneous leishmaniasis.
7 August 2020 in Research, Society and Development
Sabe-se que HIV destrói progressivamente certos glóbulos brancos do sangue chamados linfócitos CD4+. Os linfócitos ajudam a defender o corpo contra células estranhas, organismos infecciosos e câncer. Assim, as pessoas ficam vulneráveis ao ataque por muitos outros organismos infecciosos. Muitas das complicações da infecção por HIV são geralmente resultado de outras infecções e não da infecção por HIV diretamente. Com isso, a presente pesquisa teve como objetivo descrever as principais relações entre a infecção pela covid-19 em pacientes com HIV. Trata-se de uma revisão integrativa, método de pesquisa criterioso empregado para demonstrar o conhecimento produzido sobre um dado assunto ou temática. Para a realização desse estudo, foram consultadas as bases de dados: MEDLINE, LILACS, Scholar google e SCIELO. Utilizou-se os Descritores em Ciências da Saúde (DeCS) de forma associada: HIV, AIDS, COVID-19, complicação e Infecções por vírus. Após a aplicação dos critérios de inclusão, restaram 8 estudos. Os estudos incluídos foram tabelados e foram feitas revisões críticas e corroborativas entre cada um deles. A COVD-19 é uma doença grave e todas as pessoas que vivem com HIV devem tomar todas as medidas de prevenção recomendadas para minimizar a exposição e prevenir a infecção pelo vírus SARS-CoV-2. Como na população em geral, pessoas idosas vivendo com HIV ou pessoas vivendo com HIV com problemas cardíacos ou pulmonares podem estar em maior risco de serem infectadas pelo vírus e de apresentarem sintomas mais graves.