About 1.5 million new cases of cutaneous leishmaniasis and 500,000 new cases of visceral leishmaniasis occur each year around the world. For over half a century, the clinical forms of the disease have been treated almost exclusively with pentavalent antimonial compounds. In this review, we describe the arsenal available for treating Leishmania infections, as well as recent advances from research on plants and synthetic compounds as source drugs for treating the disease. We also review some new drug-delivery systems for the development of novel chemotherapeutics. We observe that the pharmaceutical industry should employ its modern technologies, which could lead to better use of plants and their extracts, as well as to the development of synthetic and semi-synthetic compounds. New studies have highlighted some biopharmaceutical technologies in the design of the delivery strategy, such as nanoparticles, liposomes, cochleates, and non-specific lipid transfer proteins. These observations serve as a basis to indicate novel routes for the development and design of effective anti-Leishmania drugs.

The in vitro activity of parthenolide against Leishmania amazonensis was investigated. Parthenolide is a sesquiterpene lactone purified from the hydroalcoholic extract of aerial parts of Tanacetum parthenium. This isolated compound was identified through spectral analyses by UV, infrared, 1 H and 13 C nuclear magnetic resonance imaging, DEPT (distortionless enhancement by polarization transfer), COSY (correlated spectroscopy), HMQC (heteronuclear multiple-quantum coherence), and electron spray ionization-mass spectrometry. Parthenolide showed significant activity against the promastigote form of L. amazonensis, with 50% inhibition of cell growth at a concentration of 0.37 g/ml. For the intracellular amastigote form, parthenolide reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 g/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis with gelatin as the substrate showed that the enzymatic activity of the enzyme cysteine protease increased following treatment of the promastigotes with the isolated compound. This finding was correlated with marked morphological changes induced by parthenolide, such as the appearance of structures similar to large lysosomes and intense exocytic activity in the region of the flagellar pocket, as seen by electron microscopy. These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products.

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Parthenolide previously isolated from Tanacetum vulgare was tested for its in vitro combinatory effect with benznidazole against Trypanosoma cruzi. Parthenolide showed a strong synergistic activity against epimastigote forms, reducing 23-fold the concentration of benznidazole necessary to inhibit 50% of cell growth (IC(50) of 1.6 to 0.07 μg/ml) when in combination with parthenolide. In addition, an additive effect against trypomastigote forms (FIC 1.06), followed by an antagonistic effect on the cytotoxicity (FIC 2.36), was observed for the combination of both drugs. Parthenolide induced morphological alterations in the body shape of trypomastigote forms, causing rounding and shortening of the parasite and loss of integrity of the plasma membrane, as previously described by other workers.

The antioxidant and antibacterial activity and toxicity of natural products can change according to plant variety, as well as the part of the plant which is analyzed. In this study, peel, pulp and seed of four avocado varieties (Quintal, Fortuna, Margarida, and Hass) were analyzed for antioxidant and antibacterial properties and toxicity. There are few studies in the literature comparing these three first varieties. Antioxidant capacity was measured using the DPPH (2,2-diphenyl-1-picrylhydrazil), ABTS [2,2'-azino-bis- (3-ethylbenzothiazoline-6-sulfonic acid)], and FRAP (Ferric Reducing Ability Power) methods, along with the content of phenolic compounds and flavonoids. Principal component analysis was applied for antioxidant tests. Antibacterial activity against food pathogens was assessed by the minimum inhibitory concentration and minimum bactericidal concentration tests. Toxicity was evaluated against Artemia salina and also by hemolytic activity. The ethanolic extract of Quintal variety peel presented the greatest antioxidant and antibacterial activity. This same extract showed no toxicity in the preliminary tests, and shows great potential for food industry application as an additive.

BackgroundLeishmania amazonensis infection results in diverse clinical manifestations: cutaneous, mucocutaneous or visceral leishmaniasis. The arsenal of drugs available for treating Leishmania infections is limited. Therefore, new, effective, and less toxic leishmaniasis treatments are still needed. We verified cell death in amastigote forms of Leishmania amazonensis induced by the sesquiterpene lactone parthenolide.ResultsThe tested compound was able to concentration-dependently affect axenic and intracellular amastigotes, with IC50 values of 1.3 μM and 2.9 μM, respectively after 72 h incubation. No genotoxic effects were observed in a micronucleus test in mice. Parthenolide induced morphological and ultrastructural changes in axenic amastigotes, including a loss of membrane integrity, swelling of the mitochondrion, cytoplasmic vacuoles, and intense exocytic activity in the region of the flagellar pocket. These results led us to investigate the occurrence of autophagic vacuoles with monodansylcadaverine and the integrity of the plasma membrane and mitochondrial membrane potential using flow cytometry. In all of the tests, parthenolide had positive results.ConclusionsOur results indicate that the antileishmanial action of parthenolide is associated with autophagic vacuole appearance, a reduction of fluidity, a loss of membrane integrity, and mitochondrial dysfunction. Considering the limited repertoire of existing antileishmanial compounds, the products derived from medicinal plants has been one the greatest advances to help develop new chemotherapeutic approaches.

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Resumo A erva-mate possui compostos biologicamente ativos com aplicação industrial. Cafeína, rutina e ácido clorogênico presentes neste produto possuem atividade antioxidante e o último ainda é antimicrobiano. Este estudo objetivou avaliar a atividade biológica do extrato de erva-mate e quantificar compostos bioativos, bem como aplicar o extrato em hambúrguer de peixe para determinar seu poder conservante. A atividade antioxidante foi avaliada por DPPH (2,2-difenil-1-picrihidrazila) e FRAP (poder de redução do ferro). Foram quantificados compostos fenólicos totais e flavonoides por espectrofotometria, e cafeína, rutina e ácido clorogênico, por cromatografia líquida de ultraeficiência. A atividade antimicrobiana foi determinada pela concentração inibitória mínima (CIM). Testaram-se associações de extrato com o conservante sintético butil-hidroxi-anisol (BHA). Hambúrgueres de peixe foram incorporados com extrato de erva-mate e foram feitas análises de composição centesimal, oxidação lipídica e microbiológica por 28 dias. O extrato apresentou para DPPH IC50 de 7,91 µg mL-1, FRAP de 4.922,67 µmol de Fe (II) g-1, 104,54 EAG g-1 de fenólicos totais, 23,11 EQ g-1 de flavonoides e 49,6, 34,5 e 23,1 mg g-1 de ácido clorogênico, cafeína e rutina, respectivamente. O extrato mostrou CIM de 10, 5 e 10 mg mL-1 contra Escherichia coli, Staphylococcus aureus e Salmonella enterica, respectivamente. A combinação de extrato com BHA reduziu a quantidade de conservante sintético para a mesma atividade antioxidante e mostrou caráter aditivo para S. aureus. Os hambúrgueres de peixe com 1% de extrato ou com BHA exibiram diferença estatística na contagem de mesófilos em relação ao controle. Assim, observou-se que o extrato de erva-mate apresentou atividade biológica e o crescimento de mesófilos foi inibido nos hambúrgueres de peixe incorporados com BHA ou 1% de extrato, de forma que os compostos fenólicos quantificados seriam os prováveis agentes conservantes.