Potential Activity of Micafungin and Amphotericin B Co-Encapsulated in Nanoemulsion against Systemic Candida auris Infection in a Mice Model.

The Candida auris species is a multidrug-resistant yeast capable of causing systemic and lethal infections. Its virulence and increase in outbreaks are a global concern, especially in hospitals where outbreaks are more recurrent. In many cases, monotherapy is not effective, and drug combinations are opted for. However, resistance to antifungals has increased over the years. In view of this, nanoemulsions (NEs) may represent a nanotechnology strategy in the development of new therapeutic alternatives. Therefore, this study developed a co-encapsulated nanoemulsion with amphotericin B (AmB) and micafungin (MICA) (NEMA) for the control of infections caused by C. auris. NEs were developed in previous studies. Briefly, the NEs were composed of a mixture of 10% sunflower oil and cholesterol as the oil phase (5:1), 10% Polyoxyethylene (20) cetyl ether (Brij® 58) and soy phosphatidylcholine as surfactant/co-surfactant (2:1), and 80% PBS as the aqueous phase. The in vivo assay used BALB/c mice weighing between 25 and 28 g that were immunosuppressed (CEUA/FCF/CAr n° 29/2021) and infected with Candida auris CDC B11903. The in vivo results show the surprising potentiate of the antifungal activity of the co-encapsulated drugs in NE, preventing yeast from causing infection in the lung and thymus. Biochemical assays showed a higher concentration of liver and kidney enzymes under treatment with AmB and MICAmB. In conclusion, this combination of drugs to combat the infection caused by C. auris can be considered an efficient therapeutic option, and nanoemulsions contribute to therapeutic potentiate, proving to be a promising new alternative.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Plumbagin: A Promising In Vivo Antiparasitic Candidate against Schistosoma mansoni and In Silico Pharmacokinetic Properties (ADMET).

Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus Schistosoma spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of Schistosoma-resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus Plumbago, has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo schistosomicidal potential of PLUM against Schistosoma mansoni and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato-Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against S. mansoni, acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET.

Microparticles in the Development and Improvement of Pharmaceutical Formulations: An Analysis of In Vitro and In Vivo Studies.

Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1-1000 µm) are widely used as drug delivery systems, because they offer higher therapeutic and diagnostic performance compared to conventional drug delivery forms. These systems can be manufactured with many raw materials, especially polymers, most of which have been effective in improving the physicochemical properties and biological activities of active compounds. This review will focus on the in vivo and in vitro application in the last decade (2012 to 2022) of different active pharmaceutical ingredients microencapsulated in polymeric or lipid matrices, the main formulation factors (excipients and techniques) and mostly their biological activities, with the aim of introducing and discussing the potential applicability of microparticulate systems in the pharmaceutical field.

Safety Evaluation of Goat Milk Added with the Prebiotic Inulin Fermented with the Potentially Probiotic Native Culture Limosilactobacillus mucosae CNPC007 in Co-culture with Streptococcus thermophilus QGE: Analysis of Acute and Repeated Dose Oral Toxicity.

Despite functional goat milk products having emerged due to their importance for human nutrition and health, few studies have assessed the safety of consumption of goat dairy products containing potentially probiotic autochthonous lactic acid bacteria supplemented with prebiotic carbohydrates. Aiming this field, this study evaluated the safety of goat's milk fermented with Streptococcus thermophilus QGE, the autochthonous Limosilactobacillus mucosae CNPC007 culture, and the prebiotic inulin, through single- and repeated-dose oral toxicity tests (SDT and RDT, respectively) in animals. Ten female Swiss Webster mice were used for SDT evaluation - 2 groups, SDTc (20 mL/kg of filtered water) and SDTt (20 mL/kg of fermented milk) - and 40 Wistar rats for RDT - RDT3, RDT6, and RDT12 (treated with fermented milk at doses of 3 mL/kg, 6 mL/kg, and 12 mL/kg, respectively) and also RDTc (12 mL/kg of filtered water). For SDT, no signs of mortality or toxicity were observed, and the animals maintained the expected weight gain and feed intake. The RDT trials did not show mortality or signs of toxicity, as well as no change in body weight and organs, in the hematological and biochemical parameters, and also in relation to morphology and histology. Since the fermented milk did not cause any toxic effect in the conditions evaluated, it can be said that its no-adverse effect level (NOAEL) was considered to be higher than 20 mL/kg/day. Thus, the fermented milk with L. mucosae CNPC007 and inulin was considered to be of low toxicity, safe for use in rodents, and allowed for use in further studies.

Protective effect of Lactiplantibacillus plantarum LP5 in a murine model of colonisation by Campylobacter coli DSPV458.

Thermotolerant Campylobacter species are the leading cause of foodborne bacterial diarrheal disease worldwide. Campylobacter coli, abundant in pigs and pork products, have been identified as a source of human infection. In this study, we propose the use of Lactiplantibacillus plantarum LP5 as a probiotic to reduce colonisation of this intestinal pathogen in a murine colonisation model of C. coli DSPV458. Six-week-old adult female Balb/cCmedc mice were housed in groups: Control, Campy and Pro-Campy. Control and Pro-Campy groups received antibiotics for 5 days and the Campy group for 12 days. Pro-Campy group was inoculated for 7 days with 8.78 log10 cfu total of L. plantarum LP5 suspended in De Man, Rogosa and Sharpe broth. All groups were inoculated with 6.72 log10 cfu of C. coli DSPV458 suspended in brain heart infusion broth. L. plantarum LP5 was recovered only in the Pro- Campy group. C. coli DSPV458 was recovered at higher levels in the Control and Campy groups. The differences with the Pro-Campy group were significant. As regards faeces, Control and Campy groups reached 7.41 and 7.84 log10 cfu/g, respectively, and the Pro-Campy group only 4.62 log10 cfu/g. In the caecum, Control and Campy groups reached 8.01 and 9.26 log10cfu/g, respectively, and the Pro-Campy group only 4.51 log10 cfu/g. In the ileum, Control and Campy groups reached 3.43 and 3.26 log10 cfu/g, respectively, and the Pro-Campy group did not show detectable levels. The reduction of C. coli DSPV458 in the Pro-Campy group compared to the Control group in faeces, caecum and ileum was 99.55, 99.98 and 100%, respectively. Animals were maintained under normal health conditions, and haematological parameters were within the standard values for Balb/cCmedc. The incorporation of a probiotic generated a protective effect in the mice colonisation model. The protective effect would also apply to intestinal colonisation by indigenous enterobacteria. Therefore, the strategy used in this study is of great importance to understand the protection mechanisms in a murine model, as well as its application in food-producing animals.

An appraisal of the scientific current situation and new perspectives in the treatment of cutaneous leishmaniasis.

Leishmaniasis is a Neglected Tropical Diseases caused by protozoan parasites of the genus Leishmania. It is a major health problem in many tropical and subtropical regions of the world and can produce three different clinical manifestations, among which cutaneous leishmaniasis has a higher incidence in the world than the other clinical forms. There are no recognized and reliable means of chemoprophylaxis or vaccination against infections with different forms of leishmaniasis. In addition, chemotherapy, unfortunately, remains, in many respects, unsatisfactory. Therefore, there is a continuing and urgent need for new therapies against leishmaniasis that are safe and effective in inducing a long-term cure. This review summarizes the latest advances in currently available treatments and improvements in the development of drug administration. In addition, an analysis of the in vivo assays was performed and the challenges facing promising strategies to treat CL are discussed. The treatment of leishmaniasis will most likely evolve into an approach that uses multiple therapies simultaneously to reduce the possibility of developing drug resistance. There is a continuous effort to discover new drugs to improve the treatment of leishmaniasis, but this is mainly at the level of individual researchers. Undoubtedly, more funding is needed in this area, as well as greater participation of the pharmaceutical industry to focus efforts on the development of chemotherapeutic agents and vaccines for this and other neglected tropical diseases.

5-lipoxygenase- and Glucocorticoid-dependent eosinophilia in a novel surgical model in mice.

BACKGROUND: Subcutaneous implants of heat-coagulated egg white (egg white implants, EWI) induce intense local eosinophilia and prime for hyperreactivity following airway ovalbumin challenge. The roles of allergen sensitization, surgical trauma-induced glucocorticoids, and the 5-lipoxygenase (5-LO) pathway were hitherto unexplored in this model, in which quantitative recovery and large-scale purification of the eosinophils from the inflammatory site for functional and immunopharmacological studies are difficult to achieve. METHODS: We overcame this limitation by shifting the implantation site to the peritoneal cavity (EWIp), thereby enabling quantitative leukocyte retrieval. RESULTS: By day 7 post-surgery, eosinophil counts reached ~ 30% of all leukocytes recovered. Eosinophilia was prevented by: a) induction of allergen-specific oral tolerance to ovalbumin, the main allergen in egg white; b) inactivation of the 5-lipoxygenase pathway; c) blockade of endogenous glucocorticoid signaling by pretreatment with metirapone plus mifepristone before surgery. Highly purified eosinophils (~99% pure) could be obtained from the peritoneal exudate of EWIp-carrier mice in 2 simple, antibody-free steps. Preparative-scale yields, suitable for most biochemical, pharmacological, and molecular applications, were routinely obtained, and could be further enhanced through addition of pre-or post-surgery immunization steps (active or adoptive). The recovered eosinophils were fully functional in vivo, as demonstrated by the transfer of purified eosinophils into eosinophil-deficient Δdbl-GATA-1-KO mice, which upon subsequent challenge with eotaxin-1 present secondary accumulation of neutrophils, but not of mononuclear phagocytes. CONCLUSION: These findings document glucocorticoid-, allergen- and 5-lipoxygenase-dependent eosinophilia, which makes EWIp carriers an abundant source of pure, nontransgenic eosinophils for immunopharmacological studies.

An Overview of the Compounds Tested In Vivo for Leishmania spp. of the Last 5 Years.

BACKGROUND: Leishmaniasis, a still important public health problem, exhibits environmental risk factors such as massive migrations, urbanization, and deforestation. WHO research for Leishmaniasis is mainly focused on the development of new tools, such as diagnostic tests, drugs, and vaccines. During the drug development strategy, only a few compounds were promising and call for further study after the in vitro and in vivo preclinical tests. OBJECTIVE: In this review, our group aimed to highlight the utmost research done during 2014 to 2019 in the fields of natural and synthetic compounds, as well as repurposed drugs and new formulations tested in vivo for Leishmania spp. METHOD: Based on the literature search, we used the databases MEDLINE, PUBMED, CAPES PERIODIC and ELSEVIER to delineate an interval of the last 5 years of research on each field. RESULTS: Among the natural compounds tested, allicin and a fraction of potato tuber extract showed the most promising antileishmanial activity. Concerning synthetic compounds, quinolines, bornyl ester, thymol, benzoxaborole and nitroimidazole derivatives exhibited encouraging results. Moreover, repositioned alternatives involved combinations with known drugs and monotherapy protocols as well. In these years, new formulations were widely assessed as drug delivery systems, such as nanoparticles, micelles and liposomes in polymer conjugations. CONCLUSION: Drug repurposing and new formulations of already-known drugs are worthwhile approaches to promptly introduce new treatment schemes to Leishmaniasis. Nevertheless, the interest in new synthetic compounds and new formulations brings light to new treatment proposals and are notable lines of research.

Bioguided chemical characterization of pequi (Caryocar brasiliense) fruit peels towards an anti-diabetic activity.

Pequi fruit peels are an underexploited source of polyphenols. The anti-diabetic potential of an extract and fractions from the peels were evaluated in a panel of assays. The extract and fractions thereof inhibited the release of cytokines involved in insulin resistance - TNF, IL-1ß, and CCL2 - by lipopolysaccharide-stimulated THP-1 cells. The ethyl acetate fraction inhibited in vitro α-glucosidase (pIC50 = 4.8 ± 0.1), an enzyme involved in the metabolization of starch and disaccharides to glucose, whereas a fraction enriched in tannins (16C) induced a more potent α-glucosidase inhibition (pIC50 = 5.3 ± 0.1). In the starch tolerance test in mice, fraction 16C reduced blood glucose level (181 ± 10 mg/dL) in comparison to the vehicle-treated group (238 ± 11 mg/dL). UPLC-DAD-ESI-MS/MS analyses disclosed phenolic acids and tannins as constituents, including corilagin and geraniin. These results highlight the potential of pequi fruit peels for developing functional foods to manage type-2 diabetes.

Garlic passion fruit (Passiflora tenuifila Killip): Assessment of eventual acute toxicity, anxiolytic, sedative, and anticonvulsant effects using in vivo assays.

Several Passiflora species are known for their sedative and anxiolytic properties. However, the functional properties of Passiflora tenuifila Killip are still unexplored. The objective of this work was to evaluate the phenolic composition and acute toxicity, anxiolytic, sedative, and anticonvulsant effects using in vivo assays. The whole fruit (peel, pulp, and seed) was lyophilized and used for all assays. LC-MS showed 19 phenolic compounds, tentatively identified as flavonoids and phenolic acids. Acute treatment with single doses of up to 2000 mg kg-1 in Wistar rats showed no signs of mortality or toxicity over 14 days. The assay of functional effects was performed with Swiss mice, four groups, received by gavage, doses of P. tenuifila (200 or 400 mg kg-1 body weight), water, and diazepam (as negative and positive control), and behavior tests were performed after 60 min of the treatments. The animals treated with P. tenuifila fruit showed a significant decrease in locomotor activity, indicating a sedative and anxiolytic activity. No significant changes were observed in the rotarod apparatus, suggesting that the P. tenuifila fruit did not cause muscle relaxation. The 400 mg kg-1 dose of P. tenuifila exerted a protective effect against pentylenetetrazole-induced seizures, decreasing the severity and not causing the death of the animals. In conclusion, P. tenuifila showed no acute toxicity and had a promising effect as an anxiolytic agent, hypnotic-sedative and anticonvulsant, which could be related to its composition of flavonoids and phenolic acids.

Supramolecular cyclodextrin-based metal-organic frameworks as efficient carrier for anti-inflammatory drugs.

Drug delivery systems have been used to reduce adverse effects and improve the efficacy of therapies. Drug carriers have been developed over the years, but they have limitations. γ-cyclodextrin-based metal-organic frameworks (γ-CD-MOF) have significant advantages due to their biocompatibility and environmental safety, besides crystallinity and porosity. Herein, γ-CD-MOFs were synthesised with different metals as nodes and investigated. Uniform mesoporous γ-CD-MOFs were obtained and showed an absence of toxicity in HepG2 and Caco-2 cells. The longer controlled release was verified for γ-CD-MOFs, with a maximum of 62% released in 12 h. An inflammation experiment was performed in mice and activity equivalent to the positive control was verified. γ-KCD-MOFs and γ-NaCD-MOFs reached activity after 6 h of administration, however this happened after 24 h in γ-FeCD-MOFs, being more effective than the positive control. Considering the ability for drug entrapment, easy preparation and controlled release, this class of material allows potential applications in drug delivery systems.

Schistosoma mansoni: In vivo evaluation of Phyllanthus amarus hexanic and ethanolic extracts.

Human schistosomiasis is an important neglected tropical disease caused by blood flukes of the genus Schistosoma and is responsible for more than 280,000 deaths annually. Treatment for this disease relies currently on a single drug, praziquantel (PZQ). Concerns regarding PZQ resistance and insensitivity of juvenile schistosomes have increased the interest in resorting to medicinal plants for alternative drug therapies. This study aimed to perform an in vivo schistosomicidal activity evaluation of crude hexanic (HE) and ethanolic (EE) extracts obtained from Phyllanthus amarus in mice infected with Schistosoma mansoni (BH strain). Mice were treated orally with a single dose of 100 or 250 mg/kg, on two different infection periods, 30 and 45 days post-infection (dpi). Parameters such as worm recovery, faecal egg count, intestinal tissue egg count and liver histopathology were evaluated. Treatment against young adult (30 dpi) and adult (45 dpi) worms were more effective compared to the control group treated with PZQ. At a concentration of 250 mg/kg (30 dpi) EE showed a 54.4% female reduction and a 61.2% total worm reduction whilst at a concentration of 100 mg/kg (45 dpi) HE showed a 40.6% female worm reduction and a 45.3% total worm reduction. Histopathological examination showed a granuloma decrease in both number and size for groups treated with 250 mg/kg of HE (45 dpi) or EE (30 or 45 dpi). From these results, it can be concluded that both hexanic and ethanolic extracts have antischistosomal activities, however, act differently according to the parasites age. The schistosomicidal activity results in groups treated 30 days post infection is extremely important since praziquantel does not show activity against the juvenile forms of Schistosoma.

Ocorrência e distribuição de BanLec em cultivares de banana e avaliação da sua atividade imunomoduladora in vivo / Occurrence and distribution of BanLec in banana cultivars and evaluation of its immunomodulatory activity in vivo

Lectinas são proteínas cuja principal característica é a de se ligar específica e reversivelmente a carboidratos. BanLec é a lectina presente na polpa de bananas, que se liga especificamente a manose e glicose, e é capaz de induzir a proliferação de células T, podendo estimular a resposta imune. Existem indícios de que o teor de BanLec pode variar dependendo do estádio de amadurecimento e do tipo de cultivar, o que pode afetar a quantidade de BanLec existente na fruta quando consumida in natura e a possível resposta imune frente ao consumo de banana. Por este motivo, um dos objetivos desse trabalho foi determinar os teores e a atividade hemaglutinante de BanLec em extratos de farinha de banana verde, além de bananas das cultivares Pacovan, Figo, Terra, Mysore e Nanicão, nos estádios de maturação verde e maduro, e submetidas a tratamento com 1-MCP e baixa temperatura (para cv. Nanicão). Com vista a atender ao objetivo de avaliar seus efeitos imunomoduladores in vivo, a BanLec foi purificada da cultivar Nanicão e administrada por via oral a camundongos BALB/c. Os ensaios de atividade hemaglutinante dos extratos de banana apontaram para maior quantidade de BanLec no fruto maduro, quando comparado ao verde, e ausência dessa proteína na cultivar Figo. Os parâmetros imunológicos analisados após administração de BanLec aos camundongos demonstram que a resposta imune gerada após ingestão de BanLec é dose dependente, além disso, a administração de 50 µg de BanLec aos animais foi capaz de modular citocinas importantes na resposta imunológica, provavelmente causando um efeito que pode ser interpretado como mais protetor do que patogênico. Com base nos resultados obtidos, podemos concluir que existem diferenças nos teores de BanLec dependendo da cultivar e estádio de maturação analisado, sendo que essa proteína não está presente na polpa de todas as variedades de banana e finalmente, que ela tem grande potencial imunomodulador in vivo, uma vez que ativou citocinas de resposta anti-inflamatória

Lectins are proteins which bind specifically and reversibly to carbohydrates. BanLec is the lectin present in banana pulp, and it binds to mannose and glucose, being capable of inducing T-cell proliferation, and to stimulate the immune response. There are some evidence that the amount of BanLec may vary depending on the maturation stage of the fruit and the cultivar (cv.), which may affect the amount of BanLec and the possible immune response after consumption of banana. Thus, this study aimed to evaluate the amount of BanLec and its hemagglutinating activity in crude extracts of bananas from cultivars Pacovan, Figo, Terra, Mysore and Nanicão, in both unripe and ripe maturation stage, and also fruits which were treated with 1-MCP and low temperature. In addition, in order to access their immunomodulatory effects in vivo, BanLec was purified by affinity chromatography and administered orally to BALB/c mice. The hemagglutinating activity assays indicate higher amount of BanLec in ripe fruit. Moreover, the possible was undetectable in the pulp of banana Figo. The immunological parameters of mice orally fed with BanLec showed that the immunological response is dependent on the amount of protein administrated, in agreement to previous in vitro studies. Besides, 50 µg of BanLec, were able to modulate some cytokines in immune response, causing an effect that seems to be more protective than pathogenic. We conclude that there are important differences in amount of BanLec depending on the cultivar and the maturation stage, and BanLec has a dose-dependent immunomodulatory effect in vivo

Effect of antioxidant potential of tropical fruit juices on antioxidant enzyme profiles and lipid peroxidation in rats.

Fruits are a rich source of a variety of biologically active compounds that can have complementary and overlapping mechanisms of action, including detoxification, enzyme modulation and antioxidant effects. Although the effects of tropical fruits have been examined individually, the interactive antioxidant capacity of the bioactive compounds in these formulations has not been sufficiently explored. For this reason, this study investigated the effect of two tropical fruit juices (FA and FB) on lipid peroxidation and antioxidant enzymes in rats. Seven groups, with eight rats each, were fed a normal diet for 4 weeks, and were force-fed daily either water (control), 100, 200, or 400 mg of FA or FB per kg. The results showed that the liver superoxide dismutase and catalase activities (FA200), erythrocytes glutathione peroxidase (FB400) and thiobarbituric acid-reactive substances (FB100, FA400, FB200, FB400) were efficiently reduced by fruit juices when compared with control; whereas HDL-c increased (FB400).