RESUMO
BACKGROUND: Coumarins, also known as benzopyrones, are plant-derived products with several pharmacological properties, including antioxidant and anti-inflammatory activities. Based on the wide distribution of coumarin derivatives in plant-based foods and beverages in the human diet, our objective was to evaluate both the antioxidant and intestinal anti-inflammatory activities of six coumarin derivatives of plant origin (scopoletin, scoparone, fraxetin, 4-methyl-umbeliferone, esculin and daphnetin) to verify if potential intestinal anti-inflammatory activity was related to antioxidant properties. METHODS: Intestinal inflammation was induced by intracolonic instillation of TNBS in rats. The animals were treated with coumarins by oral route. The animals were killed 48 h after colitis induction. The colonic segments were obtained after laparotomy and macroscopic and biochemical parameters (determination of glutathione level and myeloperoxidase and alkaline phosphatase activities) were evaluated. The antioxidant properties of these coumarins were examined by lipid peroxidation and DPPH assays. RESULTS: Treatment with esculin, scoparone and daphnetin produced the best protective effects. All coumarin derivatives showed antioxidant activity in the DPPH assay, while daphnetin and fraxetin also showed antioxidant activity by inhibiting lipid peroxidation. Coumarins, except 4-methyl-umbeliferone, also showed antioxidant activity through the counteraction of glutathione levels or through the inhibition of myeloperoxidase activity. DISCUSSION: The intestinal anti-inflammatory activity of coumarin derivatives were related to their antioxidant properties, suggesting that consumption of coumarins and/or foods rich in coumarin derivatives, particularly daphnetin, esculin and scoparone, could prevent intestinal inflammatory disease.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite/metabolismo , Colo/efeitos dos fármacos , Cumarínicos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Compostos de Bifenilo/metabolismo , Colite/etiologia , Colite/prevenção & controle , Colo/metabolismo , Cumarínicos/uso terapêutico , Esculina/farmacologia , Esculina/uso terapêutico , Glutationa/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/prevenção & controle , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Picratos/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Umbeliferonas/farmacologia , Umbeliferonas/uso terapêuticoRESUMO
Recognizing the invasive potential of the dermatophytes and understanding the mechanisms involved in this process will help with disease diagnosis and with developing an appropriate treatment plan. In this report, we present the histopathological, microbiological and immunological features of a model of invasive dermatophytosis that is induced by subcutaneous infection of Trichophyton mentagrophytes in healthy adult Swiss mice. Using this model, we observed that the fungus rapidly spreads to the popliteal lymph nodes, spleen, liver and kidneys. Similar to the human disease, the lymph nodes were the most severely affected sites. The fungal infection evoked acute inflammation followed by a granulomatous reaction in the mice, which is similar to what is observed in patients. The mice were able to mount a Th1-polarized immune response and displayed IL-10-mediated immune regulation. We believe that the model described here will provide valuable information regarding the dermatophyte-host relationship and will yield new perspective for a better understanding of the immunological and pathological aspects of invasive dermatophytosis.
Assuntos
Antígenos de Fungos/imunologia , Interações Hospedeiro-Patógeno/imunologia , Interleucina-10/imunologia , Tinha/imunologia , Trichophyton/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Injeções Subcutâneas , Interleucina-10/metabolismo , Rim/imunologia , Rim/microbiologia , Fígado/imunologia , Fígado/microbiologia , Linfonodos/imunologia , Linfonodos/microbiologia , Masculino , Camundongos , Pele/imunologia , Pele/microbiologia , Baço/imunologia , Baço/microbiologia , Células Th1/imunologia , Fatores de Tempo , Tinha/microbiologia , Tinha/patologia , Trichophyton/crescimento & desenvolvimento , Trichophyton/fisiologiaRESUMO
ETHNOPHARMACOLOGY RELEVANCE: Different plant species from Cordia genera are used in folk medicine as anti-inflammatory medication throughout the tropical and subtropical regions of the world. In Brazil, Cordia verbenacea is a medicinal plant known as "erva-baleeira". The alcoholic extracts, decoctions and infusions with leaves of C. verbenacea are used in Brazilian traditional medicine for treatment of cough, pneumonia, parasitic diseases and, especially, the inflammatory processes. Anti-inflammatory activity was already demonstrated; however, molecular mechanisms of action are not completely understood. Considering the importance of histamine in early events of inflammation and in allergic diseases, we evaluated the effect of ethanol extract of leaves of C. verbenacea on histamine release (in vitro and in vivo studies) from different types of mast cells induced by chemical agents using several species of rodents. MATERIALS AND METHODS: The extraction and quantification of histamine were performed by using an automatic fluorometric continuous flow system. RESULTS: The extract of C. verbenacea (30 µg/ml) reduced the in vitro secretion of histamine from rat mast cells induced by ionophore A23187, concanavalin A and compound 48/80, respectively, to 22.1 ± 2.2%, 24.3 ± 2.5% and 21.4 ± 2.1%. At the same concentration, the extract also inhibited the secretion of histamine from mast cells of guinea pig induced by ionophore A23187 to 33.3 ± 2.2%, and mast cells of hamster induced by ionophore A23187 and concanavalin A to 15.8 ± 2.5% and 10.8 ± 2.6%, respectively. The oral treatment with the extract (300 mg/kg) also inhibited the secretion of histamine induced by A23187 about to 36.3 ± 3.2% in rats. CONCLUSIONS: C. verbenacea inhibits the in vitro secretion of histamine from mast cells of different animal species, as well as the secretion of mast cells from animals treated with the extract, which gives not only the proven anti-inflammatory effect of the plant, but also anti-allergic effect, opening new possibilities for future anti-allergic herbal medicine.
Assuntos
Cordia/química , Mastócitos/metabolismo , Extratos Vegetais/farmacologia , Animais , Etanol/química , Cobaias , Liberação de Histamina/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Ratos , Ratos WistarRESUMO
The present study aimed to clarify the role of mast cells in colitis with relapse induced in Wistar rats by trinitrobenzenosulphonic acid. Colitis induction increased the histamine concentration in the colon, which peaked on day 26. The number of mast cells, probably immature, was ten times higher on day 8. Different from animals infected with intestinal parasites, after colitis remission, mast cells do not migrate to the spleen, showing that mast cell proliferation presents different characteristics depending on the inflammation stimuli. Treatment with sulfasalazine, doxantrazole, quercetin, or nedocromil did not increase the histamine concentration or the mast cell number in the colon on day 26, thereby showing absence of degranulation of these cells. In conclusion, although mast cell proliferation is associated with colitis, these cells and their mediators appear to play no clear role in the colitis with relapses.
Assuntos
Colite/induzido quimicamente , Colite/patologia , Mastócitos/patologia , Ácido Trinitrobenzenossulfônico/farmacologia , Animais , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Fármacos Gastrointestinais/farmacologia , Histamina/metabolismo , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Microscopia , Nedocromil/farmacologia , Ratos , Ratos Wistar , Sulfassalazina/farmacologia , Tioxantenos/farmacologia , Xantonas/farmacologiaRESUMO
Coumarins represent an important class of phenolic compounds with multiple biological activities, including inhibition of lipidic peroxidation and neutrophil-dependent anion superoxide generation, anti-inflammatory and immunosuppressor actions. All of these proprieties are essential for that a drug may be used in the treatment of inflammatory bowel disease. The present study examined intestinal anti-inflammatory activity of coumarin and its derivative, the 4-hydroxycoumarin on experimental ulcerative colitis in rats. This was performed in two different experimental settings, i.e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the coumarin and 4-hydroxycoumarin, at doses of 5 and 25 mg/kg, significantly attenuated the colonic damage induced by trinitrobenzenesulphonic acid (TNBS) in both situations, as evidenced macroscopically, microscopically and biochemically. This effect was related to an improvement in the colonic oxidative status, since coumarin and 4-hydroxycoumarin prevented the glutathione depletion that occurred as a consequence of the colonic inflammation.