Bidens pilosa L: efeitos protetores na inflamação intestinal

Inflammatory Bowel Disease (IBD) comprises basically two distinct diseases: Crohn's disease (CD) and Ulcerative Colitis (UC), both characterized by chronic inflammation of the intestine, with exacerbation periods followed by long intervals of remission of symptoms. Despite being subject of research for decades, its etiology is still unknown and a single agent or isolated mechanism is not enough to produce or trigger the disease. The difficulty in effectively treat all patients based on the poor response to drug and in the several side effects that the treatments presents, supports the search for new sources of compounds useful in the treatment and prevention of IBD. Among the various strategies available, the research of medicinal plants shows promise. Bidens pilosa L., Asteraceae, is a weed with wide distribution and occurrence in some countries and is known in Brazil as picão-preto. Although it is considered a weed without economic importance, has been used in various populations with medical purpose and its application in various diseases may be due to its chemical composition rich in phytol and polyunsaturated fatty acid (palmitic acid, oleic acid and linoleic acid) compounds known to have anti-inflammatory and/or antioxidants effects. In the present study the supercritical extract of Bidens pilosa L. was able to reduce the levels of pro-inflammatory mediators, such as MPO, IL-1β and TNF-α associated with modulation of anti-inflammatory factors such as IL-10, both in the preventive and curative protocols. Also modulates gene expression of genes related to inflammation and mucosal protection, such as HSP70 and MUC. In addition to the biochemical changes might notice a histological improvement in colonic samples analyzed by electron microscopy. Together with structural changes was an increase in the production and secretion of mucin, mucosal protective agents. Thereby, B.pilosa extract is an important source of compounds which may ...A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Colite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e um único agente ou mecanismo isolado não parecem ser suficientes para produzir ou desencadear a doença. A dificuldade em se tratar de forma efetiva todos os pacientes com DII em função da baixa resposta aos fármacos associada a diversos efeitos colaterais corrobora a busca de novas fontes de compostos úteis no tratamento e prevenção da DII. Entre as várias estratégias disponíveis, a pesquisa de plantas medicinais se mostra promissora. Bidens pilosa L., família Asteraceae, é uma erva daninha com ampla distribuição e ocorrência em diversos países, sendo conhecida no Brasil como picão-preto. Apesar de ser considerada uma erva daninha sem importância econômica tem sido utilizada em várias populações com finalidade medicinal e sua aplicação em diversas enfermidades pode ser devido a sua composição química rica em phytol e ácido graxos poli-insaturados (ácido palmítico, ácido oleico ácido linoleico), compostos com efeitos anti-inflamatórios e/ou antioxidantes. No presente trabalho o extrato supercrítico de Bidens pilosa L. foi capaz de reduzir os níveis de mediadores pró-inflamatórios, como MPO, IL-1β e TNF-α além de modular fatores anti-inflamatórios como IL-10 tanto no protocolo preventivo quanto no curativo. Modulou também a expressão gênica de genes relacionados à inflamação e proteção da mucosa, como HSP70 e MUC. Além das alterações bioquímicas pôde-se notar uma melhora histológica em amostras de cólon analisadas por microscopia eletrônica. Associada a alterações estruturais ocorreu um ...Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

HSP70, heparanase e HPRT participam da resposta inflamtória intestinal induzida por TNBS em ratos

A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e a principal limitação no entendimento dos mecanismos fisiopatológicos desta doença é a disponibilidade de modelos experimentais adequados que mimetizem o caráter crônico e de recidiva da DII em humanos e que possam ser de baixo custo, reprodutível, fácil de induzir e que apresente características clínicas e histopatológicas, respostas terapêuticas e mediadores inflamatórios similares ao que ocorre com a doença em humanos. Dentre os vários modelos experimentais disponíveis, o modelo de colite induzida por ácido trinitrobenzenosulfônico (TNBS) em ratos tem sido considerado o mais adequado para a avaliação de novos fármacos, assim como aquele que melhor mimetiza esta doença em humanos. Assim sendo, a caracterização do papel de diferentes mediadores do processo inflamatório intestinal neste modelo permitiria a determinação de novos alvos terapêuticos, assim como geraria informações importantes da fisiopatologia desta doença. Neste sentido, o presente projeto teve como objetivo determinar a participação da HSP70, Heparanase e HPRT, mediadores do processo inflamatório intestinal em humanos, na fase aguda do processo inflamatório intestinal induzido TNBS em ratos, assim como estudar os efeitos de fármacos das três principais classes farmacológicas usadas no tratamento da DII em humanos, os aminossalicilatos (sulfassalazina), os glicocorticóides (prednisolona) e os imunomoduladores (azatioprina) sobre esses mediadores. Este estudo demonstrou que HSP70, Heparanase...The idiopatic inflammatory bowel diseases comprise two types of chronic intestinal disorders: Crohn’s disease and ulcerative colitis that are characterized by a chronic inflammation of the intestine, with periods of remission and reactivation of the inflammatory process. Although IBD is the subject of research for several decades, its etiology remains unknown, and the major limitation to understanding the IBD pathophysiology is the availability of experimental models that mimic the chronic and relapse of human IBD. Is still important that experimental models can be inexpensive, reproducible, easy to induce and present clinical and histopathological features, therapeutic responses and inflammatory mediators similar to what occurs in humans. Among experimental models available, the model of colitis induced by trinitrobenzenesulphonic acid (TNBS) in rats has been considered the most suitable for the evaluation of new drugs, as well as the one that best mimics the disease in humans. Therefore, the involvement of different IBD mediators in this experimental model would allow the determination of new therapeutic targets, as well as generate important information on the pathophysiology of this disease. In light of this, the aim of present study was to determine the participation of HSP70, Heparanase and HPRT, mediators of intestinal inflammatory process in humans, in acute phase of inflammatory process induced by TNBS in rats, as well as, to study the effects of drugs of the three main classes used in the treatment of human IBD, i.e., aminosalicylates (sulphasalazine), glucocorticoids (prednisolone) and immunomodulators (azathioprine) on these mediators. This study showed that HSP70, Heparanase and HPRT participate as mediators of intestinal inflammation induced by TNBS since these mediators are increased in colitic animals when compared to healthy animals... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Experimental evidence of MAP kinase gene expression on the response of intestinal anti-inflammatory drugs

The etiopathogenesis of inflammatory bowel disease (IBD) is unclear and further understanding of the mechanisms that regulate intestinal barrier integrity and function could give insight into its pathophysiology and mode of action of current drugs used to treat human IBD. Therefore, we investigated how intestinal inflammation affects Map kinase gene expression in rats, and if current intestinal anti-inflammatory drugs (sulphasalazine, prednisolone and azathioprine) act on these expressions. Macroscopic parameters of lesion, biochemical markers (myeloperoxidase, alkaline phosphatase and glutathione), gene expression of 13Map kinases, and histologic evaluations (optic, electronic scanning and transmission microscopy) were performed in rats with colonic inflammation induced by trinitrobenzenesulphonic (TNBS) acid. The colonic inflammation was characterized by a significant increase in the expression of Mapk1, Mapk3 and Mapk9 accompanied by a significant reduction in the expression ofMapk6. Alterations inMapk expression induced by TNBS were differentially counteracted after treatment with sulphasalazine, prednisolone and azathioprine. Protective effects were also related to the significant reduction of oxidative stress, which was related to increase Mapk1/3 expressions, which were reduced after pharmacological treatment. Mapk1, Mapk3,Mapk6 and Mapk9 gene expressionswere affected by colonic inflammation induced by TNBS in rats and counteracted by sulphasalazine, prednisolone and azathioprine treatments, suggesting that these genes participate in the pharmacological response produced for these drugs.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Intestinal Microbiota and miRNA in IBD: A Narrative Review about Discoveries and Perspectives for the Future

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC) and comprises a chronic gastrointestinal tract disorder characterized by hyperactive and dysregulated immune responses to environmental factors, including gut microbiota and dietary components. An imbalance of the intestinal microbiota may contribute to the development and/or worsening of the inflammatory process. MicroRNAs (miRNAs) have been associated with various physiological processes, such as cell development and proliferation, apoptosis, and cancer. In addition, they play an important role in inflammatory processes, acting in the regulation of pro- and anti-inflammatory pathways. Differences in the profiles of miRNAs may represent a useful tool in the diagnosis of UC and CD and as a prognostic marker in both diseases. The relationship between miRNAs and the intestinal microbiota is not completely elucidated, but recently this topic has gained prominence and has become the target of several studies that demonstrate the role of miRNAs in the modulation of the intestinal microbiota and induction of dysbiosis; the microbiota, in turn, can regulate the expression of miRNAs and, consequently, alter the intestinal homeostasis. Therefore, this review aims to describe the interaction between the intestinal microbiota and miRNAs in IBD, recent discoveries, and perspectives for the future