RESUMO
Inflammatory bowel diseases, mainly ulcerative colitis and Crohn's disease are characterized by chronic inflammation in the intestine. Currently several therapeutic strategies available to treat inflammatory bowel diseases. Though, most treatments can be associated with serious adverse effects what justifies the search for new treatments. In this sense, we highlight the interest in herbal products rich in bioactive compounds which immunomodulatory and antioxidant properties as is the case of Bryophyllum pinnatum (Crassulaceae). This plant is used in traditional medicine in Brazil for treating inflammatory diseases. We hypothesized that hydroethanolic B. pinnatum leaf extract has intestinal anti-inflammatory effects on two experimental colitis models: 2.4-dinitrobenzene sulfonic acid (DNBS) in rats, and dextran sulfate sodium (DSS) in mice. Ultra-fast liquid chromatography method used for the quantification of the main compounds indicated good linearity, specificity, selectivity, precision, robustness and accuracy. The major flavonoids (mg/g of the extract) quantified were: quercetin 3-O-α-L-arabinopyranosyl-(1â2)-α-L-rhamnopyranoside (35.56 ± 0.086 mg/g), kaempferol 3-O-α-L-arabinopyranosyl-(1â2)-α-L-rhamnopyranoside (4.66 ± 0.076 mg/g) and quercetin-3-O-rhamnopyranoside (4.56 ± 0.026 mg/g). The results obtained in the DNBS and DSS models indicate that extract has both chemopreventive and anti-inflammatory effects, observing a significant reduction in the disease activity index score, and less macroscopic and microscopic damage. The extract promoted downregulation of Toll-like receptor and kappa B p65 nuclear factor gene expression, leading to a reduction in pro-inflammatory and oxidative mediators, chemokines, and cell adhesion molecules. This immunomodulatory property was proposed that one of the possible action mechanisms of extract. An improvement in intestinal damage was also associated with a reduction in oxidative stress and infiltration of leukocytes, as evidenced by the reduction in malonaldialdehyde and myeloperoxidase activity and increase in total glutathione in the colonic tissue. Moreover, the extract improved the cytoarchitecture of the colonic tissue and the integrity of the intestinal epithelial barrier by restoring the expression of the proteins associated with mucosa protection. In view of the beneficial effects showed by the B. pinnatum leaf extract in preclinical rodent models of colitis there is the potential to conduct some future clinical studies to ensure safe and effective development of a phytotherapeutic treatment for human inflammatory bowel diseases.
RESUMO
Ulcerative colitis (UC) is an inflammatory bowel disease with increasing incidence in the world, especially in developing countries. Although knowledge of its pathogenesis has progressed over the last years, some details require clarification. Studies have highlighted the role of microbial dysbiosis and immune dysfunction as essential factors that may initiate the typical high-grade inflammatory outcome. In order to better understand the immunopathophysiological aspects of UC, experimental murine models are valuable tools. Some of the most commonly used chemicals to induce colitis are trinitrobenzene sulfonic acid, oxazolone and dextran sodium sulfate. These may also be used to investigate new ways of preventing or treating UC and therefore improving targeting in human studies. The use of functional foods or bioactive compounds from plants may constitute an innovative direction towards the future of alternative medicine. Considering the above, this review focused on updated information regarding the 1. gut microbiota and immunopathogenesis of UC; 2. the most utilized animal models of the disease and their relevance; and 3. experimental application of natural products, not yet tested in clinical trials.
Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Microbioma Gastrointestinal , Animais , Produtos Biológicos/farmacologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Modelos BiológicosRESUMO
This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-κB p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1ß, IL-6, IL-17, TNF-α, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited anti-inflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/patologia , Intestinos/patologia , Soro do Leite/química , Animais , Anti-Inflamatórios/farmacologia , Colite/genética , Citocinas/genética , Citocinas/metabolismo , Dinitrofluorbenzeno/análogos & derivados , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Cabras , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Células RAW 264.7 , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties. PURPOSE: This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine-glycine-aspartic acid) and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. MATERIALS AND METHODS: SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered intrarectally to TNBS-induced colitic rats for 7 days. RESULTS: The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the expression of different pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6, and IL-12) and inducible nitric oxide synthase in comparison with the TNBS control group. Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1 and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN treatment. However, both treatments improved the intestinal wall integrity by increasing the gene expression of some of its markers (trefoil factor-3 and mucins). CONCLUSION: SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats, which were improved by functionalization with the RGD peptide.
Assuntos
Colite/tratamento farmacológico , Fibroínas/química , Fibroínas/farmacologia , Intestinos/efeitos dos fármacos , Nanopartículas/química , Oligopeptídeos/química , Ácido Trinitrobenzenossulfônico/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/imunologia , Colite/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fibroínas/uso terapêutico , Mucosa Intestinal/metabolismo , Intestinos/imunologia , Nanomedicina , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos WistarRESUMO
Complementary or alternative medicine is of great interest for the treatment of inflammatory bowel disease, with the aim of ameliorating the side effects of the drugs commonly used or improving their efficacy. In this study, we evaluated the ability of goat whey to prevent intestinal inflammation in the experimental model of acetic acid-induced rats and compared it to sulfasalazine. Pretreatment with goat whey (1, 2, and 4g/kg) and sulfasalazine (250mg/kg) on colitic rats improved colonic inflammatory markers, including myeloperoxidase activity, leukotriene B4 levels, as well as the production of proinflammatory cytokines IL-1ß and tumor necrosis factor-α. Furthermore, the administration of goat whey significantly reduced the colonic oxidative stress by reducing malondialdehyde levels and increased total glutathione content, a potent antioxidant peptide. The histological evaluation of the colonic specimens from colitic rats confirmed these beneficial effects, as goat whey preserved the colonic tissue, especially in those rats treated with the highest dose of goat whey or with sulfasalazine. The immunohistochemistry analysis of the colonic tissue evaluation also revealed a reduction in the expression of cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-9, together with an increased expression of suppressor of cytokine signaling-1. These results suggest that goat whey exerted a preventive effect against the intestinal damage induced by acetic acid, showing a similar efficacy to that shown by sulfasalazine, therefore making it a potential treatment for human inflammatory bowel disease.
Assuntos
Cabras/metabolismo , Ácido Trinitrobenzenossulfônico/farmacologia , Soro do Leite , Ácido Acético , Animais , Colite/induzido quimicamente , Colo , Humanos , Inflamação/metabolismo , Peroxidase/metabolismo , Ratos , Ratos WistarRESUMO
El dolor pélvico crónico es un motivo frecuente de consulta que está presente hasta en un 40% de las mujeres y que afecta de manera considerable su calidad de vida. El síndrome de congestión pélvica asociado a varices constituye un factor etiológico de esta patología; sin embargo, existe poca evidencia que describa la eficacia y seguridad de la técnica quirúrgica abierta. Este estudio evalúa los resultados clínicos de la cirugía abierta para el manejo de las várices pélvicas.Materiales y métodos: Se realizó un estudio descriptivo de corte transversal con 94 pacientes con varices gonadales, sometidas a cirugía abierta. Se evaluaron los hallazgos del método diagnóstico, los hallazgos intraoperatorios, y la evolución posoperatoria. Resultados: El 85% de las pacientes presentó reflujo bilateral y 15% reflujo unilateral. Más del 70% de las pacientes consultaron por presentar dolor pélvico mayor a seis meses, dispareunia, dismenorrea y síntomas urinarios. Se encontraron diferencias estadísticas significativas cuando se compararon los diámetros reportados en el dúplex, con los medidos intraoperatoriamente, en específico en las mediciones de la vena gonadal derecha, tanto en pacientes con reflujo unilateral (p = 0,022) como bilateral (p = 0,017). El 92% de las pacientes presentó mejoría de los síntomas posterior al tratamiento quirúrgico. Conclusiones: La ligadura de las venas ováricas por cirugía abierta es una alternativa terapéutica para el tratamiento de las várices pélvicas, con resultados que demuestran mejoría sintomática importante. El dúplex constituye un método diagnóstico útil, aunque el diámetro de las venas gonadales puede ser subestimado.
Chronic pelvic pain is a frequent condition for health care outpatient visits, which may occur in up to 40 % of women, and that significantly affects quality of life. The pelvic congestion syndrome associated with varicose veins is an etiological factor of this disease, but there is little evidence describing the efficacy and safety of the open surgical technique. This study evaluates the clinical results of open surgery for the management of pelvic varicose veins. Material and Methods: A cross sectional study with 94 patients with gonadal varix, who underwent open surgery, was conducted. We evaluated the diagnostic test findings, intra operative findings, and postoperative evolution. Results: 85 % of patients had bilateral reflux, and 15 % unilateral reflux. Over 70 % reported pelvic pain for more than six months, dyspareunia, dysmenorrhea, and urinary symptoms. Statistically significant differences were found when comparing the diameters reported in the duplex, with those measured intra-operatively, specifically of right gonadal vein, both in patients with unilateral (p = 0.022) and bilateral reflux (p = 0.017). 92% of the patients showed improvement of symptoms after surgical treatment. Conclusions: The ovarian vein ligation by open surgery is a therapeutic alternative for the treatment of pelvic varicose veins, with results demonstrating significant symptomatic improvement. The duplex is a useful diagnostic method, although the diameter of the gonadal veins may be underestimated.
A dor pélvica crônica é um motivo frequente de consulta, que está presente até em um 40% das mulheres, e que afeta de forma considerável sua qualidade de vida. A síndrome de congestão pélvica associada a varizes constitui um fator etiológico desta patologia; no entanto, existe pouca evidência que descreva a eficácia e segurança da técnica cirúrgica aberta. Este estudo avalia os resultados clínicos da cirurgia aberta para o manejo das varizes pélvicas. Materiais e métodos:: realizou-se um estudo descritivo de corte transversal com 94 pacientes com varizes gonadais, submetidas à cirurgia aberta. Avaliaram-se os achados do método diagnóstico, os achados intraoperatórios, e a evolução pós-operatória. Resultados: 85% das pacientes apresentaram refluxo bilateral, e 15% refluxo unilateral. Mais do 70% dos pacientes consultaram por apresentar dor pélvica maior a 6 meses, dispareunia, dismenorreia, e sintomas urinários. Encontraram-se diferenças estatisticamente significativas quando se compararam os diâmetros reportados no dúplex, com os medidos intraoperatoriamente, especificamente nas medições da veia gonadal direita, tanto em pacientes com refluxo unilateral (p=0.022) quanto bilateral (p= 0.017). O 92% das pacientes apresentou melhoria dos sintomas posterior ao tratamento cirúrgico. Conclusões: A ligadura das veias ovarianas por cirurgia aberta é uma alternativa terapêutica para o tratamento das varizes pélvicas, com resultados que demonstram melhoria sintomática importante. O dúplex constitui um método diagnóstico útil, ainda que o diâmetro das veias gonadais pode ser subestimado.
Assuntos
Humanos , Feminino , Varizes , Qualidade de Vida , Cirurgia Geral , Síndrome , Estudos Transversais , Dor Pélvica , Gerenciamento ClínicoRESUMO
Hot aqueous extraction of the basidiocarps of the mushroom Pleurotus sajor-caju provided a cold water-soluble, gel-like glucan, which was characterized chemically, and its effects on RAW 264.7 cell line (mouse leukaemic monocyte macrophage) activation were determined. NMR spectroscopy, HPSEC, methylation analysis, and a controlled Smith degradation showed it to have a branched structure with a (1â3)-linked ß-Glcp main-chain, substituted at O-6 by single-unit ß-Glcp side-chains, on the average of two to every third residues of the backbone, with a molar mass of 9.75 × 10(5) g mol(-1). In macrophage cell culture, the ß-glucan induced production of NO and the cytokines TNF-α, IL-1ß, these effects being very similar as those of Escherichia coli serotype 0111:B4 Sigma-Aldrich lipopolysaccharide (LPS), although not modifying the response of LPS-activated macrophages. The results suggest that the (1â3), (1â6)-linked ß-glucan from P. sajor-caju may have potential for immunological activities, although additional experiments are necessary for a better understanding of the mechanisms involved.
Assuntos
Pleurotus/química , beta-Glucanas/química , beta-Glucanas/farmacologia , Agaricales/química , Animais , Sequência de Carboidratos/fisiologia , Relação Dose-Resposta a Droga , Carpóforos/química , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/fisiologia , Camundongos , Modelos Biológicos , Células Tumorais CultivadasRESUMO
Se ha asumido el reto de pensar la formación de líderes ambientales comunitarios. En este sentido, desde: a) lo sociológico, se reflexiona sobre la cultura desde una perspectiva compleja, sobre el sujeto, la cultura y la identidad, b) lo deontológico, se piensa el tipo de sujeto que se quiere para la ciudad, además, se piensa en el perfil del líder ambiental, c) lo epistemológico, se piensa sobre los conocimientos, sentidos y acciones que pueden ser propias del líder, y sobre la dinámica a través de la cual se construyen las características del perfil, d) lo pedagógico, se propone el sentido que debe cobrar la educación y consecuentemente se propone el "Modelo para la formación de líderes ambientales comunitarios", e) desde lo didáctico, es posible proponer diversas alternativas que respondan a las necesidades de los contextos, pero articuladas a través del enfoque transversal o integrador denominado: "Formación centrada en proyectos".
The challenge of thinking Environmental Leaders Training has been assumed. In this sense from: a) the sociological viewpoint, culture is reflected as a complex perspective about the person, the culture and identity; b) from the deontological viewpoint, the type of individual who is wanted in the city, and the environmental leaders profile are considered;, c) from the epistemological viewpoint, the knowledge, feelings and actions that may be characteristic of the Leader are addressed and the dynamics through which the profile characteristics are constituted are considered;, d) from the pedagogical viewpoint, the sense that education should have is proposed and consequently the "Model for Environmental Community Leaders Training" is suggested; e) from the teaching viewpoint, it is possible to propose various options which can respond to the needs of different contexts, but articulated through a transversal or integrative approach called Project-Based Education.
Assuntos
Humanos , Educação em Saúde Ambiental , Botânica , Jardins , LiderançaRESUMO
The aim of the present study was to compare the effects of the 4-methylesculetin with those produced by prednisolone and sulphasalazine and to elucidate the mechanisms involved in its action. Colitis was induced in rat by instillation of trinitrobenzenesulphonic acid (TNBS). The colon damage was evaluated using macroscopic, microscopic and biochemical analysis. In addition, in vitro studies were performed to evaluate cytokine production in cell cultures using the murine macrophage cell line RAW264.7, mouse splenocytes and the human colonic epithelial cell line Caco-2. 4-Methylesculetin produced a reduction of the macroscopic damage score and the recovery of the intestinal cytoarchitecture. These effects were associated with a prevention of the GSH depletion and an inhibition in AP activity. After colitis relapse, 4-methylesculetin improved the colonic inflammatory status as evidenced by histological findings, with a reduction in apoptosis, as well as biochemically by inhibition of colonic myeloperoxidase, alkaline phosphatase and metalloproteinase 9 activities. Paired with this inhibitive activity, there was a decrease in malondialdehyde content and in IL-1ß levels. In vitro assays revealed that 4-methylesculetin promoted an inhibition in IL-1ß, IL-8, IL-2 and IFN-γ production in cell cultures. In conclusion, 4-methylesculetin showed similar efficacy to that obtained with either prednisolone or sulphasalazine, both in the acute phase of colitis as well as following a curative protocol. The intestinal anti-inflammatory activity by 4-methylesculetin is likely related to its ability in reduce colonic oxidative stress and inhibit pro-inflammatory cytokine production.
Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Colite/patologia , Cumarínicos/farmacologia , Prednisolona/farmacologia , Sulfassalazina/farmacologia , Umbeliferonas/farmacologia , Fosfatase Alcalina/antagonistas & inibidores , Fosfatase Alcalina/metabolismo , Animais , Anti-Inflamatórios/química , Linhagem Celular , Colite/induzido quimicamente , Cumarínicos/química , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Recidiva , Ácido Trinitrobenzenossulfônico/toxicidade , Umbeliferonas/química , Umbeliferonas/uso terapêuticoRESUMO
El reporte que se hace a través de este artículo se constituye como un caso analizado a través de una perspectiva cualitativa, mediante la cual se recupera información que da cuenta de las vivencias y formas de entender la educación ambiental de un grupo de profesionales que tiene diversas formas de aproximación a las comunidades de Bogotá. Las reflexiones y propuestas presentadas nacen a través de un proceso de formación y de acompañamiento a los participantes del Seminario Permanente de Formación de Formadores Ambientales Enrique Pérez Arbeláez. La información cualitativa, emergente de los espacios de discusión entre los participantes y el orientador, recogida por medio de estrategias como el diario de campo y guías de registro, evidencia la reflexión y la auto-evaluación como alternativas para estructurar la educación ambiental desde las particularidades de las comunidades de Bogotá.
The report presented through this article becomes a case analyzed through a qualitative approach through which information accounting for the experiences and ways to understand environmental education of a group of professionals having a diverse approach to the communities in Bogotá. The reflections and proposals presented come from an educational and accompaniment process of the participants in the Environmental Formative Influence Permanent Education Seminar "Enrique Pérez Arbeláez". The qualitative information emerging from de discussion spaces between the participants and the presenter gathered using strategies such as field journals and registry guides evidences the reflection and self-evaluation as alternatives to structure environmental education from the particularities of the communities in Bogotá.