Seaweeds have attracted special interest as good sources of sulphated polysaccharides (SP) for use in pharmaceutical industries and biotechnology. In this study, we evaluated the effects of SP from the red seaweed Gracilaria cornea (Gc-TSP) in nociceptive and inflammatory models. In mice, Gc-TSP (3, 9 or 27 mg ⁄ kg) significantly reduced nociceptive responses, as measured by the number of writhes, at all tested doses. In a formalin test, Gc-TSP significantly reduced licking time in both phases of the test at a dose of 27 mg ⁄ kg. In a hot-plate test, the antinociceptive effect was observed only in animals treated with 27 mg ⁄ kg of Gc-TSP, suggesting that the analgesic effect occurs through a central action mechanism at the highest dose. Gc-TSP (3, 9 or 27 mg ⁄ kg) caused only a slight reduction in neutrophil migration in the rat peritoneal cavity. However, lower doses of Gc-TSP (3 and 9 mg ⁄ kg) significantly inhibited paw oedema induced by carrageenan, especially at 3 hr after treatment. Reduction in oedema was confirmed by myeloperoxidase activity in the affected paw tissue. In addition, treatment (s.c.) of animals with different doses of Gc-TSP inhibited paw oedema induced by dextran within the first hour in all doses tested. After 14 consecutive days of intraperitoneal administration of Gc-TSP (9 mg ⁄ kg), we measured the wet weight of the liver, kidney, heart, spleen and thymus and performed biochemical, haematological and histopathological evaluations. No systemic damage was found. These results indicate that Gc-TSP possesses analgesic and anti-inflammatory effects and is a potentially important tool worthy of further study.Inflammation is a protective response initiated after injury through physical damage or infection by microorganisms. Consisting of both systemic and local responses, inflammation is an essential biological process with the conserved functions of eliminating the noxious factors, promoting tissue repair and wound healing and establishing memory, which enables the host to mount a faster and more specific response upon a future encounter with the relevant stimulus [1]. Tissue damage, inflammation or injury to the nervous system may result in chronic neuropathic pain characterized by increased sensitivity to painful stimuli, the perception of innocuous stimuli as painful and spontaneous pain [2].A wide variety of noxious mechanical, thermal and chemical stimuli induce a marked inhibition in the activity of spinal dorsal horn convergent neurons, and it has been suggested that supra spinal neural system mediates this inhibition control through descending pathways. The sensitization of primary afferent nociceptors is common for all inflammatory pain types, leads to a state of hyperalgesia and ⁄ or allodynia in human beings and is well described as nociception in animal models [3].The administration of non-steroidal anti-inflammatory drugs is an important tool in the suppression of the inflammatory response in a clinical context and has the ability to inhibit initial or later manifest...

The results indicate that the analgesic and anti-inflammatory effects of Cc-SP2 could be of biomedical applicability as a new, natural tool in pain and acute inflammatory conditions.

Oreochromis niloticus has skin anticoagulant glycosaminoglycans (GAGs), but their effects on thrombin generation (TG) are unknown. This study partially characterized skin GAGs and analyzed as inhibitors of TG. Papain-extraction yield of 0.1% contained two fractions separated by DEAE-cellulose chromatography, differing on charge density and carboxylated groups by a combination of agarose/polyacrylamide electrophoresis and sequential toluidine blue/stains-all staining, presenting molecular sizes ca. 40 kDa. Depolymerization of the fractions with chondroitin ABC lyase showed dermatan sulfate (DS) as the unique GAG by agarose analysis. Both activated partial thromboplastin time (APTT) and prothrombin time tests only showed anticoagulation by fractions and mammalian DS by APTT (0.61, 0.47 and 1.72 IU, respectively) against heparin (193 IU). Fractions acted concentrationdependent on both intrinsic/extrinsic pathways in TG using 60-fold diluted human plasma, with more than 50% inactivation (41.6 and 83.3 µg), whereas DS and heparin entirely abolished at low amounts. DS from O. niloticus skin blocks in vitro TG in human plasma.Key words: Cichlidae; freshwater fish; sulfated glycans; thrombosis in vitro; waster Inibição da geração de trombina por dermatam sulfato isolado da pele de Oreochromis niloticus RESUMOOreochromis niloticus possui glicosaminoglicanos (GAGs) anticoagulantes de pele, porém desconhecidos são seus efeitos sobre geração de trombina (GT). Caracterizou-se parcialmente GAGs de pele e analisou-se como inibidores de GT. Rendimento de 0,1% da extração com papaína, conteve duas frações separadas por cromatografia de DEAE-celulose, e por combinação de eletroforese de agarose/poliacrilamida e coramento sequencial azul de toluidina/"stains-all", diferiram quanto à densidade da carga e grupos carboxilados, apresentando tamanhos moleculares ca. 40 kDa. Depolimerização das frações com condroitinase ABC mostrou, por análise em agarose, dermatam sulfato (DS) como GAG único. Ambos os testes do tempo de tromboplastina parcial ativada (TTPA) e do tempo de protrombina mostraram anticoagulação, das frações e DS de mamífero, somente pelo TTPA (0,61; 0,47 e 1,72 UI, respectivamente) contra ao da heparina (193 UI). Frações atuaram sobre ambas vias intrínsica/ extrínsica dependente de concentração na GT usando plasma humano diluído 60 vezes, com inativação mais que 50% (41,6 e 83,3 µg), enquanto em quantidades baixas DS e heparina aboliram totalmente. DS da pele de O. niloticus bloqueia GT in vitro no plasma humano. Palavras-chave:Cichlidae; peixe dulcícola; glicanos sulfatados; trombose in vitro; resíduo

No abstract

The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw edema model induced in rats by different inflammatory agents (carrageenan, dextran, serotonin, bradykinin, compound 48/80 or L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously - s.c., significantly inhibited rat paw edema induced by carrageenan and dextran, as confirmed by myeloperoxidase and Evans’ blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw edema induced by histamine, compound 48/80 and L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2 mRNA and protein levels compared with those of the carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with ZnPP IX, a specific heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.

AmII has important antinociceptive and anti-inflammatory properties and represents an important therapeutic agent warranting future studies.

Seaweed lectins have been widely investigated as anti-nociceptive and anti-inflammatory agents. This study analyzed the anti-nociceptive and anti-inflammatory responses of a lectin from the green seaweed Caulerpa cupressoides (CcL) on zymosan-induced arthritis of the rat temporomandibular joint (TMJ). Rats received i.v. CcL 30 min prior to injection of zymosan (2mg/art.) or 0.9% saline into the left TMJ. Mechanical hyper-nociception was measured by the electronic von Frey method at baseline and 4h after zymosan injection. Animals were euthanized 6h after zymosan injection and the synovial fluid was collected for leukocyte counting and myeloperoxidase activity assessment. Other animals were treated with ZnPP-IX (3mg/kg; s.c.), a specific heme oxygenase-1 pathway inhibitor, and naloxone (10 μg/art.), a nonselective opioid receptor antagonist. TMJ tissues were excised to perform histopathological and immunohistochemistry analyses. CcL (0.1, 1 or 10mg/kg) significantly reduced zymosan-induced hyper-nociception (81, 83 and 89.5%, respectively) and inhibited the leukocyte influx (77.3, 80.7 and 98.5%, respectively) compared with the zymosan-only group, as confirmed by myeloperoxidase activity; however, treatment with naloxone or ZnPP-IX did not revert the effects of CcL (10mg/kg), suggesting that the naloxone-sensitive opioid and heme oxygenase-1 pathways are not involved. CcL also reduced the leukocyte influx and the expression of IL-1β and TNF-α in the TMJ, based on histopathological and immunohistochemistry analyses, respectively. Therefore, CcL reduces TMJ hyper-nociception and inflammation with a mechanism that is partially dependent on TNF-α and IL-1β inhibition. CcL reveals a potentially valuable alternative tool for future studies of TMJ disorders.

SP-Gb may be used as a tool for further investigations into the inflammatory processes associated with the hemoxigenase-1 pathway.