ABSTRACT
The present work explores the esterification reaction in the polysaccharide extracted from the seaweed Gracilaria birdiae and investigates its antioxidant potential. The reaction process was conducted with phthalic anhydride at different reaction times (10, 20 and 30 min), using a molar ratio of 1:2 (polymer: phthalic anhydride). Derivatives were characterized by FTIR, TGA, DSC and XRD. The biological properties of derivatives were investigated by assays of cytotoxicity and antioxidant activity (2,2-diphenyl-1-picrylhydroxyl - DPPH and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt - ABTS). The results obtained by FT-IR confirmed the chemical modification, there was a reduction related to the presence of carbonyl and hydroxyl groups when compared to the in nature polysaccharide spectrum. TGA analysis showed a change in the thermal behavior of the modified materials. X-ray diffraction, it was shown that the in nature polysaccharide appeared as an amorphous material, while the material obtained after the chemical modification process had increased crystallinity, due to the introduction of phthalate groups. For the biological assays, it was observed that the phthalate derivative was more selective than the unmodified material for the murine metastatic melanoma tumor cell line (B16F10), revealing a good antioxidant profile for DPPH and ABTS radicals.
Subject(s)
Antineoplastic Agents , Gracilaria , Animals , Mice , Antioxidants/chemistry , Phthalic Anhydrides , Galactans , Spectroscopy, Fourier Transform Infrared , Antineoplastic Agents/chemistry , Polysaccharides/chemistryABSTRACT
Leishmaniases are infectious diseases caused by protozoa of the genus Leishmania, that may have different clinical manifestations. First line drugs used in the treatment of leishmaniosis are high costly, and are very aggressive requiring medical monitoring. Thus new therapeutic alternatives are needed and, in this context, natural products have been considered as a source of new antileishmania agents. Riparins are alkamides found in the unripe fruits of Aniba riparia. Several biological activities are described for this group of compounds, such as antimicrobial and antiparasitic potential. The objective of this work was to evaluate the anti-leishmania activity riparin E (Rip-E) in vitro, against promastigotes and internalized amastigotes of Leishmania amazonensis. Rip-E was able to inhibit promastigote cell growth (IC50 4.7 µg/ml) and to reduce the percentage of macrophages infected with amastigotes, reducing its infectivity (survival index) (IC50 1.3 µg/ml). The cytotoxicity against BALB/c murine macrophages was also assessed (CC50 50.6 µg/ml) and the selectivity index was 38.9. Rip-E also demonstrated immunomodulatory activity, evidenced by the increase of the phagocytic capacity and lysosomal activity. However, Rip-E did not affect directly the production of nitric oxide. These results suggest that Rip-E has antileishmania potential, by both its direct inhibitory effect and its ability to activate macrophages.
Subject(s)
Antiprotozoal Agents/pharmacology , Immunomodulation , Leishmania/drug effects , Macrophages/drug effects , Animals , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Cell Proliferation/drug effects , Female , Leishmania/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Molecular Structure , Parasitic Sensitivity TestsABSTRACT
In the present work, we investigated the minimal inhibitory concentration (MIC) against fungal strains (Fonsecaea pedrosoi, Microsporum canis, Candida albicans, Cryptococcus neoformans), and cytotoxicity to normal cell lines for modified red angico gum (AG) with eterifying agent N-chloride (3-chloro-2-hydroxypropyl) trimethylammonium (CHPTAC). Quaternized ammonium groups were linked to AG backbone using N-(3-chloro-2-hydroxypropyl) trimethylammonium chloride. The chemical features of the quaternized gum derivatives (QAG) were analyzed by: FTIR, elemental analysis, Zeta potential and gel permeation chromatography. The angico quaternizated gum presented a degree of substitution (DS) of 0.22 and Zeta potential of +36.43. For the antifungal test, it was observed that unmodified gum did not inhibit fungal growth. While, QAG inhibited the growth of most fungi used in this study. By AFM technique QAG interacted with the fungal surface, altering wall roughness significantly. The probable affinity of fragments of the QAG structure for the fungal enzyme 5I33 (Adenylosuccinate synthetase) has been shown by molecular docking. Low cytotoxicity was observed for polymers (unmodified gum and QAG). The results demonstrate that the quaternized polymer of AG presented in this study is a quite promising biomaterial for biotechnological applications.
Subject(s)
Antifungal Agents , Cytotoxins , Enzyme Inhibitors , Fabaceae/chemistry , Fungal Proteins , Fungi/enzymology , Molecular Docking Simulation , Polysaccharides , Animals , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Cytotoxins/chemistry , Cytotoxins/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/chemistry , HEK293 Cells , Humans , Ligases/antagonists & inhibitors , Ligases/chemistry , Mice , Polysaccharides/chemistry , Polysaccharides/pharmacologyABSTRACT
Sterculia gums, as karaya and chicha gum, are complex branched and polydisperse heteropolysaccharides which can have their applications extended by improving their characteristics through chemical modifications. The objective of this work was to increase the antimicrobial activity of karaya and chicha gum through chemical modification with maleic anhydride. The incorporation of anhydride in the gum structure was confirmed by the characterization techniques. The derived biopolymers were synthesized and characterized by FTIR, X-ray diffraction, Thermogravimetric analysis and elemental analysis. Antimicrobial activity was evaluated against the Staphylococcus aureus strain (ATCC 25923). Mammalian cytotoxicity assays were also performed by MTT and hemolysis tests. The derivatives showed excellent antibacterial action inhibiting almost 100% of bacterial growth and did not present significant cytotoxicity in mammalian cells. The results showed that the derivatives are promising for biomedical applications aiming the control of infectious diseases caused by S. aureus.
Subject(s)
Anti-Bacterial Agents/pharmacology , Maleic Anhydrides/chemistry , Plant Gums/pharmacology , Sterculia/chemistry , Animals , Anti-Bacterial Agents/chemistry , Female , Karaya Gum/chemistry , Karaya Gum/pharmacology , Male , Mice , Microbial Sensitivity Tests , Microbial Viability/drug effects , Plant Gums/chemistry , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Thermogravimetry , Toxicity Tests , X-Ray DiffractionABSTRACT
This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103-104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.
Subject(s)
Anacardium/chemistry , Microscopy, Atomic Force , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biocompatible Materials/chemistry , Cell Line, Tumor , Humans , Magnetic Resonance Spectroscopy , Plant Gums/chemistryABSTRACT
Leptospirosis is a worldwide zoonosis whose transmission is interlinked by multiple factors in the man-animal-ecosystem interface. This study aimed to evaluate the risk factors for the occurrence of anti-Leptospira antibodies in dogs in the capital Teresina (PI), and to determine their spatial distribution. Five hundred fifty-eight dog blood samples were submitted to the Microscopic Serum Agglutination (MSA) test. We applied semi-structured questionnaires to dog owners and obtained the area of residence for projection in geographical maps. Serum prevalence was 13.8%, in which the most common serovar was icterohaemorrhagiae, with 49.2%. Dogs with street access, failure to collect food bowl and low income of owners were risk factors. There was a higher number of seropositive dogs in the rainy season, with 87.1%, which is a probable risk factor for the occurrence of cases. The distribution of seropositive dogs was widely spread in the city, with predominance of cases in anthropized areas. These risk factors favor the occurrence of anti-Leptospira antibodies in dogs that are agent maintenance sources in the city and reinforce the need for epidemiological and environmental surveillance to prevent leptospirosis.
A leptospirose é uma zoonose mundial cuja transmissão está interligada por múltiplos fatores na interface homem-animal-ecossistema. Objetivou-se com este estudo avaliar os fatores de risco para a ocorrência de anticorpos antiLeptospira em cães na capital Teresina (PI), e determinar sua distribuição espacial. Amostras sanguíneas de 558 cães foram submetidas à prova de Soroaglutinação Microscópica (SAM). Aplicou-se questionários semiestruturados para os proprietários dos cães e obteve-se a localização geográfica da residência para a sua projeção em mapas geográficos. A soroprevalência foi de 13,8%, no qual o sorogrupo mais frequente foi o Icterohaemorrhagiae com 49,2%. Foram considerados fatores de risco os cães com acesso à rua, o não recolhimento da vasilha de alimento e a baixa renda dos proprietários. Foi observado maior número de cães soropositivos no período chuvoso com 87,1%, sendo um possível fator de risco para a ocorrência de casos. A distribuição dos cães soropositivos na cidade se apresentou de forma dispersa, com predominância dos casos em área antropizada. Esses fatores de risco favorecem a ocorrência de anticorpos antiLeptospiraem cães, os quais podem ser fontes de manutenção do agente na cidade e reforça a necessidade de vigilância epidemiológica e ambiental na prevenção da leptospirose.
Subject(s)
Antibodies, Bacterial/blood , Dog Diseases/epidemiology , Leptospira/immunology , Leptospirosis/epidemiology , Agglutination Tests , Animals , Brazil/epidemiology , Dog Diseases/microbiology , Dogs , Female , Humans , Income , Male , Prevalence , Risk Factors , Seroepidemiologic Studies , Surveys and QuestionnairesABSTRACT
Resumo A leptospirose é uma zoonose mundial cuja transmissão está interligada por múltiplos fatores na interface homem-animal-ecossistema. Objetivou-se com este estudo avaliar os fatores de risco para a ocorrência de anticorpos antiLeptospira em cães na capital Teresina (PI), e determinar sua distribuição espacial. Amostras sanguíneas de 558 cães foram submetidas à prova de Soroaglutinação Microscópica (SAM). Aplicou-se questionários semiestruturados para os proprietários dos cães e obteve-se a localização geográfica da residência para a sua projeção em mapas geográficos. A soroprevalência foi de 13,8%, no qual o sorogrupo mais frequente foi o Icterohaemorrhagiae com 49,2%. Foram considerados fatores de risco os cães com acesso à rua, o não recolhimento da vasilha de alimento e a baixa renda dos proprietários. Foi observado maior número de cães soropositivos no período chuvoso com 87,1%, sendo um possível fator de risco para a ocorrência de casos. A distribuição dos cães soropositivos na cidade se apresentou de forma dispersa, com predominância dos casos em área antropizada. Esses fatores de risco favorecem a ocorrência de anticorpos antiLeptospiraem cães, os quais podem ser fontes de manutenção do agente na cidade e reforça a necessidade de vigilância epidemiológica e ambiental na prevenção da leptospirose.
Abstract Leptospirosis is a worldwide zoonosis whose transmission is interlinked by multiple factors in the man-animal-ecosystem interface. This study aimed to evaluate the risk factors for the occurrence of anti-Leptospira antibodies in dogs in the capital Teresina (PI), and to determine their spatial distribution. Five hundred fifty-eight dog blood samples were submitted to the Microscopic Serum Agglutination (MSA) test. We applied semi-structured questionnaires to dog owners and obtained the area of residence for projection in geographical maps. Serum prevalence was 13.8%, in which the most common serovar was icterohaemorrhagiae, with 49.2%. Dogs with street access, failure to collect food bowl and low income of owners were risk factors. There was a higher number of seropositive dogs in the rainy season, with 87.1%, which is a probable risk factor for the occurrence of cases. The distribution of seropositive dogs was widely spread in the city, with predominance of cases in anthropized areas. These risk factors favor the occurrence of anti-Leptospira antibodies in dogs that are agent maintenance sources in the city and reinforce the need for epidemiological and environmental surveillance to prevent leptospirosis.
Subject(s)
Humans , Animals , Male , Female , Dogs , Dog Diseases/epidemiology , Leptospira/immunology , Leptospirosis/epidemiology , Antibodies, Bacterial/blood , Brazil/epidemiology , Agglutination Tests , Seroepidemiologic Studies , Prevalence , Surveys and Questionnaires , Risk Factors , Dog Diseases/microbiology , IncomeABSTRACT
Platonia insignis Mart., popularly known as "bacurizeiro," is used in traditional medical practices based on its diverse biological properties. This study was aimed at evaluating the antileishmanial effects of the ethanol extract (EtOH-Ext), hexane fraction (Hex-F), and its main isolated Lupeol obtained from stem barks of P. insignis against Leishmania (Leishmania) amazonensis, as well as their cytotoxicity and possible mechanisms of action. The EtOH-Ext, Hex-F, and Lupeol inhibited the growth of L. amazonensis promastigote forms at IC50 of 174.24, 45.23, and 39.06 µg/mL, respectively, as well as L. amazonensis axenic amastigote forms at IC50 of 40.58, 35.87, and 44.10 µg/mL, respectively. The mean cytotoxic concentrations for macrophages (CC50) were higher than those for amastigotes (341.95, 71.65, and 144.0 µg/mL, resp.), indicating a selective cytotoxicity towards the parasite rather than the macrophages. Interestingly, all treatments promoted antileishmanial effect against macrophage-internalized amastigotes at concentrations lower than CC50. Furthermore, increases of lysosomal volume of macrophages treated with EtOH-Ext, Hex-F, and Lupeol were observed. On the other hand, only Lupeol stimulated increase of phagocytic capability of macrophages, suggesting this compound might be characterized as the biomarker for the antileishmanial effect of P. insignis stem bark, as well as the involvement of immunomodulatory mechanisms in this effect.
ABSTRACT
Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Ellagic Acid/pharmacology , Gallic Acid/pharmacology , Leishmaniasis, Cutaneous/drug therapy , Animals , Antiprotozoal Agents/administration & dosage , Calcium/metabolism , Dose-Response Relationship, Drug , Ellagic Acid/administration & dosage , Female , Gallic Acid/administration & dosage , Immunologic Factors/administration & dosage , Immunologic Factors/pharmacology , Leishmania major/drug effects , Leishmania major/isolation & purification , Leishmaniasis, Cutaneous/parasitology , Macrophages/drug effects , Macrophages/parasitology , Male , Mice , Mice, Inbred BALB CABSTRACT
Leishmaniasis is an infectious disease complex caused by protozoa from the Leishmania genus, which presents a broad spectrum of clinical manifestations: cutaneous, mucocutaneous and visceral forms. The current treatments are unsatisfactory considering that few drugs are available and present some level of toxicity. Many lignans and neolignans have been used for the development of new antileishmania drugs. The capability in vitro of the neolignan 2,3-dihydrobenzofuran (2,3-DBF), a commonly found constituent of propolis and other plants, to inhibit the growth of promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis was investigated. The cytotoxicity of this compound was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test in BALB/c murine macrophages and human erythrocyte lysis assay. The 2,3-DBF was active against promastigote (IC50 =1.042 µM) and amastigote (IC50 =1.43 µM) forms, indicating a potent antileishmanial effect. There was no evidence of cytotoxicity to macrophages or erythrocytes at concentrations ranging from 13 to 0.5 µM, after 48 hr of exposure. The antileishmanial activity is probably mediated by the activation of macrophages, because treatment with 2,3-DBF increases both phagocytic and lysosomal activities, as well as the nitrite (NO2- ) levels. These results suggest that 2,3-DBF may be a potential candidate for the development of a new promising antileishmanial drug. Further studies are needed to determine its potential in vivo effect as well as additional mechanisms underlying the antileishmanial and immunomodulatory activities.
Subject(s)
Antiprotozoal Agents/pharmacology , Benzofurans/pharmacology , Leishmania/drug effects , Lignans/pharmacology , Animals , Antiprotozoal Agents/adverse effects , Benzofurans/adverse effects , Erythrocytes/drug effects , Hemolysis/drug effects , Humans , Hydroxylation , Inhibitory Concentration 50 , Leishmania/growth & development , Leishmania/physiology , Lignans/adverse effects , Lysosomes/drug effects , Lysosomes/enzymology , Macrophage Activation/drug effects , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/parasitology , Mice, Inbred BALB C , Nitric Oxide/agonists , Nitric Oxide/metabolism , Osmolar Concentration , Phagocytosis/drug effectsABSTRACT
The American Cutaneous Leishmaniasis (ACL) is an infectious disease that can be fatal. The first line of treatment is pentavalent antimonies. However, due to its potential to develop resistance, Amphotericin B (AmB) started to be used as an alternative medicine. Current treatments are limited, a fact that has led to a growing interesting in developing new therapies. This study aims to evaluate the therapeutic potential in vivo of an amphotericin B + oleic acid (OA) emulgel in the treatment of cutaneous leishmaniasis in an experimental model. Strains of Leishmania major MHOM/IL/80/Friendlin of Leishmania major were used. The animals were inoculated subcutaneously. After the development of leishmanial, nodular or ulcerative lesions, the animals were divided into three groups (control, Group A and Group B) and treated twice a day for twelve days. The weight of the animals was measured and the size of the lesions was observed. A histopathological analysis was performed with skin fragments of lesions and with the spleen of animals treated with different treatments (emulgel, AmB 3% emulgel and AmB 3% plus OA 5% emulgel). It was observed that when subjected to treatment with AmB 3% emulgel during the study period using both formulations, with enhancer and without enhancer, ulcerative lesions regress gradually or even complete cure. The quantification of the average number of parasites recovered from the inoculation site was made after the treatment in each group and the differences were considered significant. The treatment with AmB 3% and OA 5% emulgel had the best in vivo therapeutic response, showing good prospects for cutaneous leishmaniasis therapy as an alternative therapy.
