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Chronic myeloid leukemia (CML) is a myeloproliferative disease, characterized by the presence of the oncogene BCR-ABL. Imatinib mesylate (IMA) is the first line treatment for CML, and some treatment resistance has been reported. Natural products are rich sources of bioactive compounds with biological effects, opening a possibility to alter cell susceptibility to drugs such as imatinib. Herein, we evaluated the interference of betulinic acid and ursolic acid in glycoprotein P (P-gp) activity and the possible synergistic effect when associated with IMA by the Chou-Talalay method. Ursolic acid presented an IC50 of 14,0µM and 19,6 µM for K562 and Lucena 1, respectively, whilst betulinic acid presented an IC50 of 8.6 µM and 12.5µM, for these cell lines. Evaluation of the combination of terpenoids and imatinib mesylate revealed that ursolic acid or betulinic acid acts in synergism with IMA, as indicated by the combination indexes (CI<1). Analysis of annexin V labelling demonstrated that combination of IMA with betulinic acid enhances the inhibition on cell proliferation via apoptosis pathway, with caspases 3/7 activation after 24 hours of treatment, and inhibition of the STAT5/Survivin pathway, decreasing cell viability. The combination of natural products and IMA on a multidrug-resistant leukemia cell line is a promising strategy for CML treatment.
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OBJECTIVE AND DESIGN: Methyl gallate (MG) is a prevalent polyphenol in the plant kingdom, which may be related to the effects of several medicinal plants. Although it is widely reported that polyphenols have therapeutic effects, there are few studies demonstrating that MG has anti-inflammatory action. This study aimed to investigate the molecular mechanism behind the anti-inflammatory activity of MG and its effect on hyperalgesia. METHODS: Swiss mice were pretreated orally with different doses of MG and subjected to i.pl. injection of zymosan to induce paw edema. RAW264.7 macrophages and BMDMs stimulated with different TLR agonists such as zymosan, LPS, or Pam3CSK4 were used to investigate the molecular mechanisms of MG RESULTS: MG inhibits zymosan-induced paw edema and hyperalgesia and modulates molecular pathways crucial for inflammation development. Pretreatment with MG inhibited cytokines production and NF-κB activity by RAW 264.7 cells stimulated with zymosan, Pam3CSK4 or LPS, but not with PMA. Moreover, pretreatment with MG decreased IκB degradation, nuclear translocation of NF-κBp65, c-jun and c-fos and ERK1/2, p38 and JNK phosphorylation. CONCLUSION: Thus, the results of this study demonstrate that MG has a promising anti-inflammatory effect and suggests an explanation of its mechanism of action through the inhibition of NF-κB signaling and the MAPK pathway.
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Antiinflamatorios no Esteroideos/farmacología , Ácido Gálico/análogos & derivados , Inflamación/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , FN-kappa B/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Citocinas/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Masculino , Ratones , Células RAW 264.7 , ZimosanRESUMEN
Methyl gallate (MG) is a prevalent phenolic acid in the plant kingdom, and its presence in herbal medicines might be related to its remarkable biological effects, such as its antioxidant, antitumor, and antimicrobial activities. Although some indirect evidence suggests anti-inflammatory activity for MG, there are no studies demonstrating this effect in animal models. Herein, we demonstrated that MG (0.7-70 mg/kg) inhibited zymosan-induced experimental arthritis in a dose-dependent manner. The oral administration of MG (7 mg/kg) attenuates arthritis induced by zymosan, affecting edema formation, leukocyte migration, and the production of inflammatory mediators (IL-1ß, IL-6, TNF-α, CXCL-1, LTB4, and PGE2). Pretreatment with MG inhibited in vitro neutrophil chemotaxis elicited by CXCL-1, as well as the adhesion of these cells to TNF-α-primed endothelial cells. MG also impaired zymosan-stimulated macrophages by inhibiting IL-6 and NO production, COX-2 and iNOS expression, and intracellular calcium mobilization. Thus, MG is likely to present an anti-inflammatory effect by targeting multiple cellular events such as the production of various inflammatory mediators, as well as leukocyte activation and migration.
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Ácido Gálico/análogos & derivados , Mediadores de Inflamación/farmacología , Macrófagos/efectos de los fármacos , Infiltración Neutrófila/efectos de los fármacos , Plantas Medicinales/química , Administración Oral , Animales , Artritis Experimental , Brasil , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/tratamiento farmacológico , Ácido Gálico/química , Ácido Gálico/farmacología , Inflamación/inducido químicamente , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Estructura Molecular , Óxido Nítrico Sintasa de Tipo II , Factor de Necrosis Tumoral alfa/farmacología , Zimosan/farmacologíaRESUMEN
OBJECTIVES: Zeyheria montana is a medicinal plant used in Brazilian folk medicine for treating skin affections, ulcers, inflammation and diarrhoea, and as an antisyphilitic and antiblenorrhagic agent, but little is known about its mechanisms of action. Herein, a bio-guided assay was carried out to further evaluate its antioxidant and immunomodulatory effects, and the possible benefits on experimental intestinal inflammation. METHODS: Extracts, partitions, fractions and isolated compounds were tested for inhibition of lipid peroxidation. Isolated compounds were tested in vitro for its antioxidant and immunomodulatory action prior to in-vivo evaluation in trinitrobenzenesulfonic acid-induced rat colitis. KEY FINDINGS: Two major compounds were identified in the leaf dichloromethane extract: 3'-hydroxy-5,7,4'-trimethoxyflavone and 6-hydroxy-5,7-dimethoxyflavone, which exhibited an antioxidant activity. The compounds protected the colonic glutathione levels in more than 90% despite the absence of protection against the gross macroscopic colonic damage. In addition, the compounds inhibited IL-1ß secretion by macrophages in 91.5% and 72.7% respectively, whereas both reduced IL-6 secretion in about 44.5%. CONCLUSIONS: The major active compounds from Z. montana leaves exerted antioxidant and immunomodulatory effects, endorsing the use of Z. montana in folk medicine as an anti-inflammatory agent. However, further investigation is still needed regarding medicinal plants and the identification of candidate compounds for the treatment of the inflammatory bowel diseases.
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Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Bignoniaceae/química , Colitis/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Intestinos/efectos de los fármacos , Fitoterapia , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Brasil , Colitis/inducido químicamente , Colitis/metabolismo , Flavonoides/análisis , Flavonoides/farmacología , Flavonoides/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Intestinos/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ácido TrinitrobencenosulfónicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark and fruit pulp of Hymenaea stigonocarpa Mart ex. Hayne (Fabaceae) has been popularly used to treat inflammation and gastrointestinal diseases including ulcers, diarrhea and gastric pain. The aim of this study was to investigate the intestinal anti-inflammatory activity of a methanol extract derived from the stem bark and diet with fruit pulp of Hymenaea stigonocarpa in the TNBS model of intestinal inflammation in rats. MATERIAL AND METHODS: The intestinal anti-inflammatory activity of stem bark extract (100, 200 and 400mg/kg) and fruit pulp (10% and 5% in diet) was measured against the intestinal inflammatory process induced by TNBS (trinitrobenzesulphonic acid) in rats. The protective effects were evaluated as follows: evaluation of intestinal damage (damage score, extension of lesion, colon weight/length ratio), incidence of diarrhea and adherence to adjacent organs, colon glutathione (GSH) and malondialdehyde (MDA) contents, myeloperoxidase (MPO) and alkaline phosphatase (AP) activities. In addition, in vitro studies on lipid peroxidation in rat brain membranes and phytochemical profile were performed with both stem bark and fruit pulp. RESULTS: Treatment with 100, 200 and 400mg/kg of stem bark extract and 10% fruit pulp flour showed protective effects in the TNBS-induced colon damage, which was related to inhibition of MPO and AP activities, reduction in colon MDA content, and counteraction of GSH depletion induced by inflammatory process. A concentration-dependent inhibitory effect on the lipid peroxidation in rat brain membranes for stem bark and fruit pulp was determined, with an IC50 value of 5.25 ± 0.23 µg/mL and 27.33 ± 0.09 µg/mL, respectively. Similar phytochemical composition was observed in fruit and stem bark, including mainly flavonoids, condensed tannins and terpenes. CONCLUSIONS: Stem bark extract and fruit pulp flour of Hymenaea stigonocarpa prevented TNBS-induced colonic damage in rats and this protective effect were associated to an improvement of intestinal oxidative stress. The observed anti-inflammatory and antioxidant effects may be associated to the presence of flavonoids and tannins in the stem bark and fruit pulp of Hymenaea stigonocarpa.
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Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Hymenaea/química , Inflamación/tratamiento farmacológico , Plantas Medicinales , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Colitis/inducido químicamente , Relación Dosis-Respuesta a Droga , Inflamación/inducido químicamente , Masculino , Corteza de la Planta/química , Tallos de la Planta/química , Distribución Aleatoria , Ratas , Ratas Wistar , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
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.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Colitis/metabolismo , Colon/efectos de los fármacos , Cumarinas/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Compuestos de Bifenilo/metabolismo , Colitis/etiología , Colitis/prevención & control , Colon/metabolismo , Cumarinas/uso terapéutico , Esculina/farmacología , Esculina/uso terapéutico , Glutatión/metabolismo , Inflamación/etiología , Inflamación/metabolismo , Inflamación/prevención & control , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Picratos/metabolismo , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Umbeliferonas/farmacología , Umbeliferonas/uso terapéuticoRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation of the intestinal epithelium that is driven by the intestinal immune system, oxidative stress and the loss of tolerance to the luminal microbiota. The use of dietary products containing ingredients such as fibres and carbohydrates and/or antioxidant compounds have been used as a therapeutic strategy for intestinal diseases because these products are considered effective in the modulation of the immune system and colonic microbiota. We investigated the beneficial effects of cattail rhizome flour (Typha angustifolia L.) in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. In addition, we investigated the effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone, which is a reference drug that is used for treatment of human IBD. METHODS: The present study included the preparation of flour from rhizomes of cattail (Typha angustifolia L.); an evaluation of the qualitative phytochemical profile of cattail rhizomes; an evaluation of the efficacy of cattail rhizome flour in TNBS-induced rat colitis; an evaluation of the synergistic effects of cattail rhizome flour on the intestinal anti-inflammatory activity of prednisolone; and macroscopic, clinical, biochemical, histopathological and microbiological studies to assess the healing effects of cattail rhizome flour and its synergistic effects in TNBS-induced rat colitis. The data were analysed by ANOVA, Kruskal-Wallis and χ(2) tests. RESULTS: We tested several concentrations of cattail rhizome flour and found that dietary supplementation with 10% cattail rhizome flour showed the best effects at reducing the extension of the lesion, the colon weight ratio, adherences to adjacent organs and diarrhoea. These effects were related to inhibition of myeloperoxidase (MPO) and alkaline phosphatase (AP) activities and an attenuation of glutathione (GSH) depletion. The 10% cattail rhizome flour was as effective as prednisolone, and no synergistic effects were observed. Saponins, flavonoids and coumarins were detected in the rhizome flour. No changes were observed in the total number of lactic bacteria after dietary supplementation with cattail rhizome flour. CONCLUSIONS: Dietary supplementation with 10% cattail rhizome flour and its combination with prednisolone prevent TNBS-induced colonic damage in rats, but no synergistic effects were observed. The prevention of TNBS-induced colon damage was associated with an improvement in intestinal oxidative stress, which likely resulted from the antioxidant properties of the active compounds detected in the cattail rhizome. This protective effect was not related to an improvement in lactic bacteria counts.
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Colitis/dietoterapia , Colon/efectos de los fármacos , Suplementos Dietéticos , Inflamación/prevención & control , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Typhaceae/química , Fosfatasa Alcalina/antagonistas & inhibidores , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Colitis/metabolismo , Colitis/patología , Colon/metabolismo , Colon/patología , Diarrea/tratamiento farmacológico , Diarrea/etiología , Fibras de la Dieta/farmacología , Fibras de la Dieta/uso terapéutico , Modelos Animales de Enfermedad , Harina , Glutatión/metabolismo , Inflamación/metabolismo , Inflamación/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Tamaño de los Órganos , Peroxidasa/antagonistas & inhibidores , Preparaciones de Plantas/farmacología , Prednisolona/farmacología , Prednisolona/uso terapéutico , Ratas , Ratas Wistar , Rizoma , Ácido TrinitrobencenosulfónicoRESUMEN
Background. This study was pathway of (-)-epicatechin (EC) in the prevention and treatment of intestine inflammation in acute and chronic rat models. Methods. Intestine inflammation was induced in rats using TNBS. The morphological, inflammatory, immunohistochemical, and immunoblotting characteristics of colon samples were examined. The effects of EC were evaluated in an acute model at doses of 5, 10, 25, and 50 mg/kg by gavage for 5 days. The chronic colitis model was induced 1st day, and treated for 21 days. For the colitis relapse model, the induction was repeated on 14th. Results. EC10 and EC50 effectively reduced the lesion size, as assessed macroscopically; and confirmed by microscopy for EC10. The glutathione levels were higher in EC10 group but decreased COX-2 expression and increased cell proliferation (PC) were observed, indicating an anti-inflammatory activity and a proliferation-stimulating effect. In the chronic colitis model, EC10 showed lower macroscopic and microscopic lesion scores and increase in glutathione levels. As in the acute model, a decrease in COX-2 expression and an increase in PC in EC10, the chronic model this increase maybe by the pathway EGF expression. Conclusion. These results confirm the activity of EC as an antioxidant that reduces of the lesion and that has the potential to stimulate tissue healing, indicating useful for preventing and treating intestine inflammation.
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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.
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Cordia/química , Mastocitos/metabolismo , Extractos Vegetales/farmacología , Animales , Etanol/química , Cobayas , Liberación de Histamina/efectos de los fármacos , Masculino , Extractos Vegetales/química , Ratas , Ratas WistarRESUMEN
The present study isolated three major active flavonoids, two flavones named 4',5,7-trimethoxy-luteolin (1) and 6-hydroxy-5,7-dimethoxyflavone (2) and the flavanone 5-hydroxy-6,7-dimethoxyflavanone (3) from Zeyheria montana dichloromethane leaf extract. Isolation and purification were conducted with the application of column chromatography and structures were assigned by spectral analysis. All compounds were evaluated for cytotoxic activities against human tumor cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-ADR/RES (breast expressing phenotype multiple drug resistance), 786-0 (renal), NCI-H460 (lung, non-small cells), PC-3 (prostate), OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia) in vitro. All compounds were active in different degrees on several tumor cell lines and flavanone 3 showed cytotoxicity against almost all cell lines, particularly against human NCI-ADR/RES and K562 cell lines. In conclusion, three antiproliferative compounds were isolated for the first time from Zeyheria montana and its leaves were characterized as an important source of methoxylated flavones and flavanone as potential antitumor compounds.
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Antineoplásicos Fitogénicos/uso terapéutico , Bignoniaceae/química , Flavanonas/uso terapéutico , Flavonas/uso terapéutico , Neoplasias/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Flavonas/aislamiento & purificación , Flavonas/farmacología , Flavonoides , Humanos , Estructura Molecular , Neoplasias/patología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la PlantaRESUMEN
AIM OF THE STUDY: Vochysia tucanorum is an important medicinal plant used in the Cerrado of Brazil against gastric disorders and this study reveals the pharmacological action of this traditional medicine use. MATERIALS AND METHODS: The methanolic extract (E-MeOH) and buthanolic fraction (Fr-Bu) obtained from V. tucanorum were challenged by different necrotizing agents in rodents. NO-synthase inhibitor (L-NAME) and SH blocker (NEM) were used to evaluate the participation of cytoprotective factors in E-MeOH and Fr-Bu gastroprotection. Antiulcerogenic action of V. tucanorum was evaluated in rats and mice at doses 250, 500 or 1000 mg/kg (E-MeOH) and 37.5, 75 or 150 mg/kg (Fr-Bu). RESULTS: Both E-MeOH and Fr-Bu present elevated gastroprotective action in all in vivo experimental models, without signs of acute toxicity. The mechanisms involved in the gastroprotective action of E-MeOH and Fr-Bu are related to the antioxidant activity and protection to gastric mucosa NO levels. Phytochemical investigations of Fr-Bu identified different pentacyclic triterpenoids such as betulinic acid, erythrodiol, epi-betulinic acid and mixtures of ursolic acid and oleanolic acid derivatives as the major constituents. The presence of such triterpenoids in Fr-Bu is probably related to the potent gastroprotective action of this medicinal plant species. CONCLUSION: Effectiveness in gastroprotection and the absence of acute toxicity indicate this species as a promising herbal drug that is in accordance with ethnopharmacological use against gastric disorders.
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Antiulcerosos/farmacología , Antioxidantes/farmacología , Magnoliopsida , Fitoterapia , Extractos Vegetales/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/efectos adversos , Antiulcerosos/uso terapéutico , Antioxidantes/efectos adversos , Antioxidantes/uso terapéutico , Brasil , Etilmaleimida/farmacología , Mucosa Gástrica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Triterpenos/efectos adversos , Triterpenos/farmacología , Triterpenos/uso terapéuticoRESUMEN
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.
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4-Hidroxicumarinas/farmacología , Antiinflamatorios , Colitis/tratamiento farmacológico , Cumarinas/farmacología , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/uso terapéutico , Enfermedad Aguda , Fosfatasa Alcalina/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Enfermedad Crónica , Colitis/inducido químicamente , Colitis/patología , Colon/patología , Cumarinas/química , Cumarinas/uso terapéutico , Diarrea/inducido químicamente , Diarrea/prevención & control , Fármacos Gastrointestinales/farmacología , Glutatión/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Prevención Secundaria , Sulfasalazina/farmacología , Ácido TrinitrobencenosulfónicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cordia verbenacea is a medicinal plant popularly used in Brazil as anti-inflammatory, antiulcer and anti-rheumatic agent without detailed pharmacological and toxicological studies. AIM OF THE STUDY: The study was aimed to investigate the effects of Cordia verbenacea in antiulcer, analgesic and antioxidant assays, as well as to evaluate its toxic effects and phytochemical profile. MATERIAL AND METHODS: Antiulcer activity of plant extract was evaluated using ethanol/HCl, ethanol and piroxican-induced gastric lesions methods. The pH, volume and total acid of gastric juice were determined by pylorus-ligated assay. Analgesic activity was evaluated by writhing, tail-flick and hot-plate tests. Antioxidant activity was determined by in vitro lipoperoxidation assay. Acute toxicity and number of deaths were evaluated by Hippocratic screening. RESULTS: The ethanol leaf extract shows a potent antiulcer activity in the ethanol/HCl and absolute ethanol-induced gastric lesions. The IC(50) value of plant extract on the lipid peroxidation was 76.11mug/ml. Preliminary phytochemical tests were positive for flavonoids, steroids, saponins, fixed acids, alkaloids and phenols. In the analgesic models the extract did not present any activity. CONCLUSIONS: Cordial verbenaceae showed a potent antiulcer activity at the dose of 125mg/kg and this effect may be associated with an improvement in stomach antioxidant mechanisms.