Matricaria chamomilla L. has been used for centuries in many applications, including antiparasitic activity. Leishmaniasis is a parasitic disease, with limited treatments, due to high cost and ...toxicity. Thus, there is a need to develop new treatments, and in this context, natural products are targets of these researches. We report the development of chitosan nanocapsules containing essential oil of M. chamomilla (CEO) from oil-in-water emulsions using chitosan modified with tetradecyl chains as biocompatible shell material. The nanocapsules of CEO (NCEO) were analyzed by optical microscopy and dynamic light scattering, which revealed spherical shape and an average size of 800 nm. Successful encapsulation of CEO was further confirmed by fluorescence microscopy observations taking advantage of the autofluorescence properties of CEO. The encapsulation efficiency was around 90%. The entrapment of CEO reduced its cytotoxicity towards normal cells. On the other hand, the CEO was active against promastigotes and intracellular amastigotes, exhibiting IC50 of 3.33 μg/mL and 14.56 μg/mL, respectively, while NCEO showed IC50 for promastigotes of 7.18 μg/mL and for intracellular amastigotes of 14.29 μg/mL. These results demonstrate that encapsulation of CEO in nanocapsules using an alkylated chitosan biosurfactant as a “green” stabilizer is a promising therapeutic strategy to treat leishmaniasis.
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•Development of chitosan nanocapsules containing M. chamomilla essential oil (NCEO);•NCEO were obtained from oil-in-water emulsions using an alkylated chitosan biosurfactant as a “green” stabilizer.•The present methodology enabled an entrapment efficiency of 90%.•The CEO encapsulation reduced its cytotoxicity and maintained antileishmanial activity.•The NCEO is a promising therapeutic strategy to treat leishmaniasis.
Ionized water has been reported to contribute to the tissue repair process and wound healing. Water purifiers can generate ionized water by means of activated charcoal with silver and minerals, the ...main purpose of which are to reduce microbiological and physicochemical contaminants. Moreover, when water is subjected to a magnetic field an organization of water molecules occurs due to the presence of mineral salts. The resulting water is thus more alkaline, which has been shown to be non-toxic to mice and can actually prolong survival. Cutaneous leishmaniasis is a neglected tropical disease, caused by obligate uni- and intracellular protozoa belonging to the genus Leishmania, that can manifest in the form of skin lesions. Thus, the objective of this study was to compare the evolution of disease in L. amazonensis-infected BALB/c mice that received tap water (TW) or ionized alkaline water (IAW). As a control, additional groups of mice receiving TW or IAW were also treated with the antileishmanial miltefosine. All mouse groups received either TW or IAW as drinking water 30 days prior to infection and the groups continued to receive the respective drinking water for 4 weeks, after which the blood and plasma were collected. Biochemical assays of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatinine, urea, glucose, triglycerides, and cholesterol were performed, in addition to hematology tests. There was a significant decrease in the volume of the lesion for groups that received IAW, in which the ingestion of ionized alkaline water favored the non-evolution of the lesion in the footpads of the animals. The results of the blood count and leukogram tests were within the normal values for BALB/c mice demonstrating that ionized water has no toxic effects on blood factors.
Recent advances in leishmaniasis treatment Tiuman, Tatiana S; Santos, Adriana O; Ueda-Nakamura, Tânia ...
International journal of infectious diseases,
08/2011, Letnik:
15, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Summary 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.
Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study ...investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against Leishmania amazonensis The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined. Morphological and ultrastructural alterations were examined by electron microscopy, and biochemical alterations, reflected by the mitochondrial membrane potential (ΔΨm), mitochondrial superoxide anion (O2·(-)) concentration, the intracellular ATP concentration, cell volume, the level of phosphatidylserine exposure on the cell membrane, cell membrane integrity, and lipid inclusions, were evaluated. In vivo antileishmanial activity was evaluated in a murine cutaneous leishmaniasis model. Compounds LSPN329 and LSPN331 showed significant selectivity for promastigotes and intracellular amastigotes and low cytotoxicity. In promastigotes, ultrastructural alterations were observed, including an increase in lipid inclusions, concentric membranes, and intense mitochondrial swelling, which were associated with hyperpolarization of ΔΨm, an increase in the O2·(-) concentration, decreased intracellular ATP levels, and a decrease in cell volume. Phosphatidylserine exposure and DNA fragmentation were not observed. The cellular membrane remained intact after treatment. Thus, the multifactorial response that was responsible for the cellular collapse of promastigotes was based on intense mitochondrial alterations. BALB/c mice treated with LSPN329 or LSPN331 showed a significant decrease in lesion thickness in the infected footpad. Therefore, the antileishmanial activity and mitochondrial mechanism of action of LSPN329 and LSPN331 and the decrease in lesion thickness in vivo brought about by LSPN329 and LSPN331 make them potential candidates for new drug development for the treatment of leishmaniasis.
Here, we review studies that have investigated the activity of plant-derived compounds against Trypanosoma cruzi, the etiologic agent of Chagas’ disease. In the last decade, more than 300 species ...belonging to almost 100 families have been evaluated for activity, and here we describe the compounds isolated; 85 references are cited.
Ultraviolet A (UVA) radiation, present in sunlight, can induce cell redox imbalance leading to cellular damage and even cell death, compromising skin health. Here, we evaluated the in vitro ...antioxidant and photochemoprotective effect of dithiothreitol (DTT). DTT neutralized the free radicals 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS
), 2,2-diphenyl-1-picrylhydrazyl (DPPH·), and superoxide anion (O
) in in vitro assays, as well as the ferric ion (Fe
) in the ferric reducing antioxidant power (FRAP) assay. We also evaluated the effect of DTT pre-treatment in L929 dermal fibroblasts and DTT (50 and 100 µM) led to greater cell viability following UVA-irradiation compared to cells that were untreated. Furthermore, the pre-treatment of cells with DTT prevented the increase of intracellular reactive oxygen species (ROS) production, including hydrogen peroxide (H
O
), lipid peroxidation, and DNA condensation, as well as the decrease in mitochondrial membrane potential (Δψm), that occurred following irradiation in untreated cells. The endogenous antioxidant system of cells was also improved in irradiated cells that were DTT pre-treated compared to the untreated cells, as the activity of the superoxide dismutase (SOD) and catalase (CAT) enzymes remained as high as non-irradiated cells, while the activity levels were depleted in the untreated irradiated cells. Furthermore, DTT reduced necrosis in UVA-irradiated fibroblasts. Together, these results showed that DTT may have promising use in the prevention of skin photoaging and photodamage induced by UVA, as it provided photochemoprotection against the harmful effects of this radiation, reducing oxidative stress and cell death, due mainly to its antioxidant capacity.
Quinoxalines belong to the N-containing heterocyclic compounds that stand out as having promising biological activity due to their privileged scaffold. In this work, we report the synthesis, ...antileishmanial, and antitrypanosomal properties of 46 new 2,3-disubstituted quinoxaline and 40 previously reported derivatives. Among all of the compounds screened for in vitro activity against epimastigotes and trypomastigotes of Trypanosoma cruzi and promastigotes of Leishmania amazonensis as well as mammalian toxicity on LLCMK2 cells and J774 macrophages, analogues from series 5, 6, 7, 9, 12, and 13 displayed high activity at micromolar IC50 and EC50 concentrations. Sixteen quinoxaline derivatives were selected and evaluated on T. cruzi and/or L. amazonensis amastigotes. The most active compounds were 6a-b and 7d-e, on all evolutive forms of L. amazonensis and T. cruzi evaluated with IC50 values 0.1–0.8 μM on promastigotes and epimastigotes 1.4–8.6 on amastigotes. Compounds 5k, 12b and 13a were the most selective (SI = 19.5–38.4) on amastigotes of T. cruzi. In general their activity was directly related to the methylsulfoxyl, methylsulfonyl, and amine groups as well as the presence of chorine or bromine in the molecules. The current results indicate that these quinoxaline derivatives are novel and promising agents for further development towards a treatment for Chagas’ disease and leishmaniasis.
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•Synthesized 46 new 2,3-disubstituted quinoxaline derivatives and 40 previously reported.•Evaluated cytotoxicity and activity on all evolutive forms of Trypanosoma cruzi and Leishmania amazonensis.•Analogs from groups 5, 6, 7, 12 and 13 exhibited promising activity and selectivity.•Activity related to the methylsulfoxyl, methylsulfonyl, and amine groups.
Chagas' disease is a condition caused by the protozoan Trypanosoma cruzi that affects millions of people, mainly in Latin America where it is considered endemic. The chemotherapy for Chagas disease ...remains a problem; the standard treatment currently relies on a single drug, benznidazole, which unfortunately induces several side effects and it is not successful in the cure of most of the chronic patients. In order to improve the drug armamentarium against Chagas' disease, in the present study we describe the synthesis of the compound 3-chloro-7-methoxy-2-(methylsulfonyl) quinoxaline (quinoxaline 4) and its activity, alone or in combination with benznidazole, against Trypanosoma cruzi in vitro.
Quinoxaline 4 was found to be strongly active against Trypanosoma cruzi Y strain and more effective against the proliferative forms. The cytotoxicity against LLCMK2 cells provided selective indices above one for all of the parasite forms. The drug induced very low hemolysis, but its anti-protozoan activity was partially inhibited when mouse blood was added in the experiment against trypomastigotes, an effect that was specifically related to blood cells. A synergistic effect between quinoxaline 4 and benznidazole was observed against epimastigotes and trypomastigotes, accompanied by an antagonistic interaction against LLCMK2 cells. Quinoxaline 4 induced several ultrastructural alterations, including formations of vesicular bodies, profiles of reticulum endoplasmic surrounding organelles and disorganization of Golgi complex. These alterations were also companied by cell volume reduction and maintenance of cell membrane integrity of treated-parasites.
Our results demonstrated that quinoxaline 4, alone or in combination with benznidazole, has promising effects against all the main forms of T. cruzi. The compound at low concentrations induced several ultrastructural alterations and led the parasite to an autophagic-like cell death. Taken together these results may support the further development of a combination therapy as an alternative more effective in Chagas' disease treatment.
Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of
Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal ...activity against
Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against
Candida albicans and
Candida parapsilosis, with MICs of 3.9 and 1.9 μg/ml, respectively. The combination of punicalagin and fluconazole showed a synergistic interaction. MIC for fluconazole decreased twofold when combined with the extract. The FIC index was 0.25. The synergism observed in disk-diffusion and checkerboard assays was confirmed in time-kill curves. The effect of punicalagin on the morphology and ultrastructure in treated yeast cells was examined by scanning and transmission electron microscopy. An irregular budding pattern and pseudohyphae were seen in treated yeasts. By transmission electron microscopy, treated cells showed a thickened cell wall, changes in the space between cell wall and the plasma membrane, vacuoles, and a reduction in cytoplasmic content. Since the punicalagin concentration effective in vitro is achievable in vivo, the combination of this agent with fluconazole represents an attractive prospect for the development of new management strategies for candidiasis, and should be investigated further in in vivo models.
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