RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice. MATERIAL AND METHODS: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action. RESULTS: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects. CONCLUSION: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.
Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Lectinas/farmacologia , Mucuna/química , Prostaglandinas/metabolismo , Receptores Adrenérgicos/metabolismo , Úlcera Gástrica/terapia , Animais , Etanol/efeitos adversos , Peroxidação de Lipídeos , Camundongos , Fitoterapia , Extratos Vegetais/uso terapêutico , Sementes/química , Úlcera Gástrica/induzido quimicamente , Testes de Toxicidade AgudaRESUMO
OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1ß mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg-1), DMDC (0.025, 0.25, or 2.5 µmol kg-1), biliverdin (1, 3, or 10 mg kg-1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg-1; s.c), respectively. RESULTS: Hemin (1 mg kg-1), DMDC (2.5 µmol kg-1), and BVD (10 mg kg-1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1ß mRNA expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.
Assuntos
Biliverdina/fisiologia , Monóxido de Carbono/fisiologia , GMP Cíclico , Heme Oxigenase-1/fisiologia , Canais KATP , Nociceptividade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite/induzido quimicamente , Biliverdina/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Heme Oxigenase-1/genética , Masculino , Limiar da Dor , Peroxidase/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Transtornos da Articulação Temporomandibular/induzido quimicamente , Transtornos da Articulação Temporomandibular/patologia , Gânglio Trigeminal/efeitos dos fármacos , ZimosanRESUMO
Lectins are proteins able to interact specifically and reversibly with carbohydrates. They are present in all living beings, particularly in legume seeds, which have many biological functions. The aim of this study was to isolate, characterize and verify antioxidant, anti-hemolytic, antitumor and gastroprotective activities in a lectin present in seeds of Phaseolus lunatus L. var. cascavel (PLUN). The isolation of lectin was performed by size exclusion chromatography on Sephadex G-100, which was isolated from a protein capable of agglutinating only human erythrocytes type A, being this the only inhibited haemagglutination n-acetyl-d-galactosamine. Its weight was estimated by PAGE is 128kDa. The lectin is thermostable up to 80°C and is active between pH 2-11. As 8M urea was able to denature the lectin. PLUN is a glycoprotein consisting of 2% carbohydrate and has antioxidant action with ascorbic acid equivalent antioxidant capacity (µMAA/g) of 418.20, 326 and 82.9 for total antioxidant activity, ABTS radical capture and capture of DPPH radical, respectively. The lectin has antitumor activity against melanoma derived cells at doses of 100 and 50mg/ml, reducing up to 83% tumor cells, and gastroprotective action, reducing up to 63% damaged area of ââthe stomach induced by ethanol.