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1.
Life Sci ; 272: 119194, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33609541

RESUMO

AIM: The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis. MATERIAL AND METHODS: After the induction of 6% acetic acid colitis, mice were treated with McN-A-343 0.5, 1.0, and 1.5 mg/kg or dexamethasone (DEXA, 2.0 mg/kg) or pirenzepine (PIR, 10 mg/kg; M1 mAChR antagonist). Colonic inflammation was assessed by macroscopic and microscopic lesion scores, colonic wet weight, myeloperoxidase (MPO) activity, interleukin-1 beta (IL1-ß) levels and tumor necrosis factor alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO3/NO2), mRNA expression of IKKα, nuclear factor kappa beta (NF-kB) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kB and COX-2. RESULTS: Treatment with McN-A-343 at a concentration of 1.5 mg/kg showed a significant reduction in intestinal damage as well as a decrease in wet weight, MPO activity, pro-inflammatory cytokine concentration, markers of oxidative stress and expression of inflammatory mediators. The action of the M1 agonist by the administration of pirenzepine, which promoted the blocking of the mAChR M1-mediated anti-inflammatory response, has also been proven. CONCLUSION: The results suggest that peripheral colonic M1 mAChR is involved in reversing the pro-inflammatory effect of experimentally induced colitis, which may represent a promising therapeutic alternative for patients with ulcerative colitis.


Assuntos
Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio/farmacologia , Colite Ulcerativa/tratamento farmacológico , Cloreto de (4-(m-Clorofenilcarbamoiloxi)-2-butinil)trimetilamônio/metabolismo , Animais , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/metabolismo , Colo/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Glutationa/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Agonistas Muscarínicos/farmacologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptor Muscarínico M1 , Fator de Necrose Tumoral alfa/metabolismo
2.
J Ethnopharmacol ; 248: 112303, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31614204

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: There are many reports of pharmacological activities of extracts and fractions of different vegetable-derived products in the scientific literature and in folk medicine. Ethnopharmacological use of these products by various communities continues to be extensively explored, and they account for more than half of all medications used worldwide. Polysaccharides (PLS) extracted from plants such as Morinda Citrifolia Linn present therapeutic potential in treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). AIM OF THE STUDY: To evaluate the anti-inflammatory action of Noni-PLS against the intestinal damage in UC induced by acetic acid in mice. MATERIALS AND METHODS: In acetic acid-induced colitis, the mice were treated intraperitoneally (ip) with Noni-PLS (0.1, 0.3, and 3.0 mg/kg) or subcutaneously (sc) with dexamethasone (2.0 mg/kg) 30 min before euthanasia to determine the best dose of Noni-PLS with an anti-inflammatory effect in the course of UC. The colonic tissue samples were collected for macroscopic, wet weight, microscopic and biochemical (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), nitrate/nitrite (NO3/NO2), cytokines, cyclooxygenase (COX-2) and inducible nitric oxide (iNOS)) analyses. RESULTS: Treatment with Noni-PLS reduced the intestinal damage induced by acetic acid as it reduced macroscopic and microscopic scores and the wet weight of the colon. In addition, MPO activity and levels of GSH, MDA, NO3/NO2, pro-inflammatory cytokines, and COX-2 expression reduced. CONCLUSIONS: This study suggests that Noni-PLS exhibits anti-inflammatory action against intestinal damage by reducing inflammatory cell infiltration, oxidative stress, pro-inflammatory action of cytokines, COX-2 and iNOS expression in the inflamed colon. Noni-PLS shows therapeutic potential against inflammatory disorders like UC.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Morinda , Polissacarídeos/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Frutas , Glutationa/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
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