RESUMO
p-Cymene (p-C) and rosmarinic acid (RA) are secondary metabolites that are present in medicinal herbs and Mediterranean spices that have promising anti-inflammatory properties. This study aimed to evaluate their intestinal anti-inflammatory activity in the trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. p-C and RA (25-200 mg/kg) oral administration reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. Both compounds (200 mg/kg) decreased malondialdehyde (MDA) and myeloperoxidase (MPO), restored glutathione (GSH) levels, and enhanced fluorescence intensity of superoxide dismutase (SOD). They also decreased interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, and maintained IL-10 basal levels. Furthermore, they modulated T cell populations (cluster of differentiation (CD)4+, CD8+, or CD3+CD4+CD25+) analyzed from the spleen, mesenteric lymph nodes, and colon samples, and also decreased cyclooxigenase 2 (COX-2), interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), and nuclear transcription factor kappa B subunit p65 (NFκB-p65) mRNA transcription, but only p-C interfered in the suppressor of cytokine signaling 3 (SOCS3) expression in inflamed colons. An increase in gene expression and positive cells immunostained for mucin type 2 (MUC-2) and zonula occludens 1 (ZO-1) was observed. Altogether, these results indicate intestinal anti-inflammatory activity of p-C and RA involving the cytoprotection of the intestinal barrier, maintaining the mucus layer, and preserving communicating junctions, as well as through modulation of the antioxidant and immunomodulatory systems.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Cinamatos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Cimenos/uso terapêutico , Depsídeos/uso terapêutico , Mucina-2/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cinamatos/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Cimenos/farmacologia , Depsídeos/farmacologia , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Interferon gama/genética , Interferon gama/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucina-2/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/genética , Ácido RosmarínicoRESUMO
The ethanolic extract of the leaves of Cissampelos sympodialis showed great pharmacological potential, with inflammatory and immunomodulatory activities, however, it showed some toxicological effects. Therefore, this study aims to verify the toxicological potential of alkaloids of the genus Cissampelos through in silico methodologies, to develop a method in LC-MS/MS verifying the presence of alkaloids in the infusion and to evaluate the toxicity of the infusion of the leaves of C. sympodialis when inhaled by Swiss mice. Results in silico showed that alkaloid 93 presented high toxicological potential along with the products of its metabolism. LC-MS/MS results showed that the infusion of the leaves of this plant contained the alkaloids warifteine and methylwarifteine. Finally, the in vivo toxicological analysis of the C. sympodialis infusion showed results, both in biochemistry, organ weights and histological analysis, that the infusion of C. sympodialis leaves presents a low toxicity.
Assuntos
Cissampelos/química , Extratos Vegetais/toxicidade , Administração por Inalação , Alcaloides/análise , Animais , Brasil , Cromatografia Líquida , Feminino , Masculino , Camundongos , Folhas de Planta/química , Metabolismo Secundário , Espectrometria de Massas em Tandem , Testes de ToxicidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves and roots of Cissampelos sympodialis (Menispermaceae) are used by indian tribes and in folk medicine to treat genitourinary infections, inflammation, asthma and gastrointestinal disorders. MATERIAL AND METHODS: The standardized ethanolic extract (Cs-EtOHE) and alkaloids total fraction (Cs-TAF) obtained from aerial parts of C. sympodialis were evaluated in several models of acute gastric ulcers. The antisecretory and/or neutralizing mechanisms of the gastric acid secretion, cytoprotective, antioxidant and immunoregulatory mechanisms were also evaluated. RESULTS: Cs-EtOHE and Cs-TAF presented a reduction in gastric mucosa lesions against ethanol, NSAIDs, hypothermic restraint-stress and gastric juice containment induced ulcer models. This activity is related to alkaloids present in the extract, and involves the participation of sulfhydryl compounds, nitric oxide, KATP channels, prostaglandins, decreased levels of IL-1ß and TNF-α and increased levels of GSH and IL-10. CONCLUSION: The data indicate gastroprotective activity, due to the participation of the cytoprotective, antioxidant and immunoregulatory mechanisms.