ABSTRACT
Polysaccharide from marine alga Gracilaria caudata has potential health benefits, such as anti-inflammatory, gastroprotective and antidiarrheal effects. Here, we investigated the effect of a sulfated polysaccharide from G. caudata (SP-GC) on hypernociception and inflammatory response in arthritis models. The animals received SP-GC (3, 10 or 30 mg/kg) 1 h before tibio-tarsal injection of zymosan. Hypernociception, histopathology, edema, vascular permeability, myeloperoxidase (MPO) activity, cell influx, interleukin (IL)-1ß and nitric oxide (NO) levels were evaluated in acute phase. In another protocol, animals received SP-GC (30 mg/kg) 2 h post-complete Freund's adjuvant (CFA). Hypernociception, edema and arthritis index were determined in acute, sub-chronic and chronic phases. Rota-rod test measured the motor performance. SP-GC significantly reduced, in a dose-dependent manner, the zymosan-induced hypernociception with maximal effect at 30 mg/kg. The microscopic inflammation, joint edema, MPO activity, cell influx, IL-1ß and NO levels were also reduced by SP-GC. In the CFA-induced arthritis, SP-GC inhibits the hypernociception, edema and arthritic index in acute, sub-chronic and chronic phases. SP-GC did not alter the motor performance of animals. In conclusion, SP-GC exerts protective effect in models of arthritis due to the modulation of cell influx, IL-1ß and NO levels, culminating in the reduction of hypernociception and edema.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Gracilaria/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Sulfates/chemistry , Animals , Arthritis, Experimental/drug therapy , Arthritis, Experimental/etiology , Arthritis, Experimental/pathology , Biomarkers , Capillary Permeability/drug effects , Disease Models, Animal , Edema/drug therapy , Edema/etiology , Freund's Adjuvant , Immunohistochemistry , Male , Mice , Rodentia , Zymosan/adverse effectsABSTRACT
OBJECTIVES: The aim of this study was to evaluate the anti-inflammatory effect of a sulphated polysaccharide fraction (PLS) extracted from the alga Hypnea musciformis and investigate the possible involvement of the nitric oxide (NO) pathway in this effect. METHODS: The anti-inflammatory activity of PLS was evaluated using inflammatory agents (carrageenan and dextran) to induce paw oedema and peritonitis in Swiss mice. Samples of paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity, NO3 /NO2 levels, and interleukin-1ß (IL-1ß) level. The involvement of NO in the modulation of neutrophil migration in carrageenan-induced paw oedema or peritonitis was also investigated. KEY FINDINGS: Compared with vehicle-treated mice, mice pretreated with PLS (10 mg/kg) inhibited carrageenan-induced and dextran-induced oedema; it also inhibited total and differential peritoneal leucocyte counts in a model of peritonitis. These PLS effects were reversed by l-arginine treatment and recovered with the administration of a NO synthase blocker (aminoguanidine). Furthermore, PLS reduced the MPO activity, decreased IL-1ß levels, and increased NO3 /NO2 levels in the peritoneal cavity. CONCLUSIONS: PLS reduced the inflammatory response by modulating neutrophil migration, which appeared to be dependent on the NO pathway.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Immune System Diseases/prevention & control , Inflammation/drug therapy , Leukocyte Disorders/prevention & control , Nitric Oxide/metabolism , Plant Extracts/therapeutic use , Polysaccharides/therapeutic use , Rhodophyta/chemistry , Animals , Anti-Inflammatory Agents/pharmacology , Arginine/pharmacology , Carrageenan , Dextrans , Edema/chemically induced , Edema/drug therapy , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Immune System Diseases/metabolism , Inflammation/chemically induced , Inflammation/immunology , Inflammation/metabolism , Interleukin-1beta/metabolism , Leukocyte Count , Leukocyte Disorders/metabolism , Male , Mice , Neutrophils/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitrogen Oxides/metabolism , Peritoneum/drug effects , Peritoneum/immunology , Peritoneum/metabolism , Peritonitis/chemically induced , Peritonitis/drug therapy , Peritonitis/immunology , Peritonitis/metabolism , Peroxidase/metabolism , Phytotherapy , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Signal Transduction , Sulfur Compounds/pharmacology , Sulfur Compounds/therapeutic useABSTRACT
Many algal species contain relatively high concentrations of polysaccharide substances, a number of which have been shown to have anti-inflammatory and/or immunomodulatory activity. In this study, we evaluated the anti-inflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction (PLS) extracted from the algae Gracilaria caudata. The antiinflammatory activity of PLS was evaluated using several inflammatory agents (carrageenan, dextran, bradykinin, and histamine) to induce paw edema and peritonitis in Swiss mice. Samples of the paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity or TNF-α and IL-1ß levels, respectively. Mechanical hypernociception was induced by subcutaneous injection of carrageenan into the plantar surface of the paw. Pretreatment of mice by intraperitoneal administration of PLS (2.5, 5, and 10 mg/kg) significantly and dose-dependently reduced carrageenan-induced paw edema (p < 0.05) compared to vehicle-treated mice. Similarly, PLS 10 mg/kg effectively inhibited edema induced by dextran and histamine; however, edema induced by bradykinin was unaffected by PLS. PLS 10 mg/kg inhibited total and differential peritoneal leukocyte counts following carrageenan-induced peritonitis. Furthermore, PLS reduced carrageenan-increased MPO activity in paws and reduced cytokine levels in the peritoneal cavity. Finally PLS pretreatment also reduced hypernociception 3-4 h after carrageenan. We conclude that PLS reduces the inflammatory response and hypernociception in mice by reducing neutrophil migration and cytokines concentration.
