ABSTRACT
Spirulina platensis (Spi) is a microalga presenting high contents of proteins, γ-linolenic acid, vitamins and minerals, and showing many biological activities. It is a promising drug for the treatment of diseases including diabetes. The objectives of this work were to study Spi effects on alloxan-induced diabetic rats, and associate this to its anti-inflammatory activity. The treatment with Spi (25, 50 or 100 mg/kg, p.o.) started 48 h after the alloxan injection, continuing for 5 or 10 days. Biochemical parameters were measured in sera of treated and untreated animals. The anti-inflammatory activity of Spi was assessed by the formalin test and carrageenan-induced paw edema in mice. Immunostainings for TNF-alpha were carried out in the carrageenan-induced paw edema in rats, before and after the Spi treatment, and its effect on the release of myeloperoxidase from human neutrophils was also determined. Spi decreased glycemia as well as triglyceride and total cholesterol levels of diabetic rats. Levels of urea and creatinine were also reduced, while liver transaminases were unaltered. Spi also decreased dose-dependently the 1st (neurogenic) and mainly the 2nd phase (inflammatory) of the formalin test, as well as the carrageenan-induced paw edema in mice. The anti-inflammatory effect of Spi was further confirmed by decreases in TNF-alpha immunostaining in the inflamed paw and in the myeloperoxidase release from human neutrophils. The results showed that the anti-diabetic effect of S. platensis is already manifested after a 5-day treatment. Additionally, considering the relationship between diabetes and inflammation, the microalga anti-inflammatory action may also be involved.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Biological Products/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Spirulina , Administration, Oral , Alloxan , Animals , Anti-Inflammatory Agents/pharmacology , Biological Products/pharmacology , Biomarkers/metabolism , Blood Glucose/drug effects , Blood Glucose/metabolism , Carrageenan , Cells, Cultured , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Dose-Response Relationship, Drug , Drug Administration Schedule , Edema/chemically induced , Edema/drug therapy , Edema/metabolism , Humans , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Lipid Metabolism/drug effects , Male , Mice , Neutrophils/drug effects , Neutrophils/enzymology , Pancreas/drug effects , Pancreas/metabolism , Peroxidase/metabolism , Rats , Rats, Wistar , Skin Diseases/chemically induced , Skin Diseases/drug therapy , Skin Diseases/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: The species Himatanthus drasticus is popularly known in Northeast Brazil as "janaguba" and belongs to the family Apocynaceae. The latex collected from its stem bark is used for several purposes including anti-inflammatory properties and presents among its bioactive constituents the pentacyclic triterpene lupeol. The objective of the present work was to study in vivo and in vitro the lupeol acetate (LA) isolated from the plant latex, in several models of inflammation. METHODS: Male Swiss mice (25-30 g, 6-24 animals per group) were administered with LA, 30 min before the test initiation. In the evaluation of analgesic activity the formalin test was used. The anti-inflammatory activity was evaluated by the following tests: paw edema induced by carrageenan and dextran, and the carrageenan-induced neutrophil migration into peritoneal cavities. Furthermore, the effect of LA on the myeloperoxidase release (MPO, an inflammation biomarker) from human neutrophils was also determined, as well as its antioxidant potential by the DPPH assay. RESULTS: In the formalin test, LA (10, 25 and 50 mg/kg, i.p.) inhibited both the 1st (neurogenic, 0-5 min) and mainly the 2nd (inflammatory, 20-25 min) phase. Naloxone completely reversed the LA effect, indicating the participation of the opioid system. LA also significantly inhibited carrageenan- and dextran-induced paw edemas, as well as the neutrophil migration to the peritoneal cavity evaluated by the carrageenan-induced pleurisia. In this model, the effect of a very low dose of LA (0.1 mg/kg) was potentiated by the same dose of pentoxifylline (PTX), a known TNF-alpha inhibitor. LA (25 and 50 µg/ml) was also very effective in inhibiting MPO released from stimulated human neutrophils, and significantly decreased the number of cells expressing iNOS activity in the paw of mice submitted to carrageenan-induced edema, suggesting a drug involvement with the NO system. CONCLUSIONS: The anti-inflammatory effect of LA probably involves the opioid system, as indicated by the complete blockade of the opioid antagonist naloxone. Furthermore, the LA effect was potentiated by PTX (a TNF-alpha inhibitor). LA also decreased the number of iNOS cells, suggesting the participation of pro-inflammatory cytokines and the NO system in the drug action.
