Sulfated polysaccharide from the green marine algae Caulerpa racemosa reduces experimental pain in the rat temporomandibular joint.

Temporomandibular disorder is a clinical painful condition in the temporomandibular joint (TMJ) region. The purified sulfated polysaccharide from the green marine algae Caulerpa racemosa (Cr) has provided anti-inflammatory and antinociceptive activity. This study evaluated these effects on a TMJ hypernociception model. Wistar rats (180 - 250 g) were pre-treated (i.v.) with Cr at 0.01, 0.1, or 1 mg/kg or vehicle 30 min before formalin (1.5%/50 µL, i.art.), capsaicin (1.5%/20 µL, i.art.), or serotonin (225 µg/50 µL, i.art.) in the TMJ, and nociceptive behaviors were measured for 45 or 30 min upon inflammatory stimuli. Inflammatory parameters vascular permeability assay, TNF-α, and IL-1ß by ELISA, protein expression of adhesion molecules ICAM-1 and CD55 by Western blot were assessed. The involvement of heme oxygenase-1 (HO-1) and nitric oxide (NO) pathways were assessed by pharmacological inhibition. Cr (1 mg/kg) reduced nociceptive behavior, plasmatic extravasation, TNF-α, and IL-1ß levels, as well as ICAM-1 and CD55 expression in periarticular tissues. Cr antinociceptive effect was not prevented by aminoguanidine, but ZnPP-IX did reduce its antinociceptive effect. Therefore, Cr antinociceptive and anti-inflammatory effects in this experimental model of hypernociception depended on the HO-1 pathway integrity, as well as reducing peripheral inflammatory events, e.g., TNF-α and IL-1ß cytokines levels, ICAM-1 and CD55 expression.

A lectin fraction from green seaweed Caulerpa cupressoides inhibits inflammatory nociception in the temporomandibular joint of rats dependent from peripheral mechanisms.

Temporomandibular disorders are the second most common cause of orofacial pain mediated by inflammatory compounds, which in many cases leads to chronic orofacial pain. This study assessed the antinociceptive and anti-inflammatory effects of a lectin from the green seaweed Caulerpa cupressoides (CcL) on hypernociception inflammatory in TMJ of rats and investigated the involvement of different mechanisms. Rats received i.v. CcL 30 min prior to injection of flogistic agentes or 0.9% saline into the left TMJ. Pretreatment with CcL (0. 1; 1 or 10 mg/kg) promoted a reduction (p < 0.05) of inflammatory hypernociception induced by 1.5% Formalin along with inhibition of inflammatory plasma extravasation, cytokines levels, ciclooxigenase-2, and intercellular adhesion molecule (ICAM-1). CcL was able to inhibit the nociceptive response induced by 1.5% Capsaicin, suggesting that CcL has an antinociceptive effect, acting directly on the primary nociceptive neurons. CcL also inhibited the nociceptive response induced by Carrageenan (100 µg/TMJ) or Serotonin (5-HT) (225 µg/TMJ). In conclusion, the results demonstrate that administration of CcL has a potential antinociceptive and anti-inflammatory effect, with a mechanism that is partially dependent on TNF-α, IL-1ß, COX-2 and ICAM-1 inhibition and independently from the cannabinoide and opioid system and NO/cGMP/PKG/K+ATP channel pathway.

Analgesic and anti-inflammatory actions on bradykinin route of a polysulfated fraction from alga Ulva lactuca.

We investigated structural features of polysaccharides from Ulva lactuca and their effects on the classical models of nociception and inflammation. Crude extract was obtained by enzymatic digestion and isolated by ion exchange chromatography on DEAE-cellulose. The fraction with higher yield was used in the tests (SP-Ul). Swiss mice received SP-Ul (1, 3 or 9mg/kg; i.v.), 30min prior to injection of 0.8%-acetic acid or 1%-formalin or prior to a thermal stimulus. At same doses, SP-Ul was tested on Wistar rats on paw edema elicited by different irritants (carrageenan, dextran, bradykinin, histamine or serotonin). The results of infrared characterization indicated the presence of hydroxyl groups, sulfate, uronic acid and glycosidic linkages in all SP fractions spectrums. SP-Ul decreased significantly the antinociception in response to acetic acid or formalin (second phase), but not in the hot-plate test, suggesting that its analgesia occurs through a peripheral mechanism. SP-Ul did not reduce carrageenan-induced paw edema as supported by both histological and myeloperoxidase activity assessments. However, SP-Ul (1mg/kg; s.c.) reduced dextran-elicited edema, showing vascular anti-inflammatory effect, with bradykinin as major target because it did not reduce histamine- and serotonin-induced paw edemas. Therefore, SP-Ul acts on bradykinin pathway in its antinociceptive and anti-inflammatory responses.

Antinociceptive and Anti-inflammatory Activities of the Lectin from Marine Red Alga Solieria filiformis.

Lectins are proteins that bind to specific mono- or oligosaccharides. This study aimed to evaluate the antinociceptive and anti-inflammatory effects of the lectin from the red marine alga Solieria filiformis. The animals (n = 6) were pretreated with S. filiformis lectin 30 min before they were given the nociceptive or inflammatory stimulus. The antinociceptive activity was evaluated in Swiss mice using the abdominal writhing, formalin, and hot plate tests. The anti-inflammatory properties were evaluated in Wistar rats using carrageenan-induced peritonitis and paw edema induced by different phlogistic agents. The S. filiformis lectin toxicity was assayed through its application in mice (7 days). S. filiformis lectin significantly reduced the number of abdominal writhings and reduced the paw licking time in the second phase of the formalin test (p < 0.05), but it did not prolong the reaction time in the hot plate test (p > 0.05). Furthermore, S. filiformis lectin reduced neutrophil migration in a peritonitis model and reduced paw edema induced by carrageenan, dextran, and serotonin (p < 0.05). Additionally, the administration of S. filiformis lectin resulted in no signs of systemic damage. Thus, S. filiformis lectin appears to have important antinociceptive and anti-inflammatory activities and could represent a potential therapeutic agent for future studies.

Dual effects of a lectin from the green seaweed Caulerpa cupressoides var. lycopodium on inflammatory mediators in classical models of inflammation.

OBJECTIVE: Wide biotechnological investigations of only a limited number of seaweed lectins have been performed. We previously demonstrated the anti-nociceptive and anti-inflammatory effects of a lectin isolated from the green seaweed Caulerpa cupressoides var. lycopodium (CcL). Herein, we further studied the mechanisms of action of CcL. METHODS: Classical acute inflammation models induced by different flogistic agents were used to evaluate the anti-inflammatory action of CcL. CcL was injected locally into the rat paw to verify a possible pro-inflammatory outcome. RESULTS: CcL (0.1, 1 or 10 mg/kg; i.v.) reduced the carrageenan-induced rat paw edema and neutrophilic infiltration, which was not altered by either mucin (inhibitor of CcL carbohydrate-binding site) or ZnPP-IX (specific HO-1 inhibitor). Immunohistochemical analyses showed that CcL (1 mg/kg) reduced the expression of the cytokines IL-1ß, TNF-α, IL-6 and COX-2. CcL (0.1, 1 or 10 mg/kg) inhibited dextran, and CcL (1 mg/kg) inhibited histamine-induced rat paw edema. Both effects were reversed by mucin inhibition. CcL (1 mg/kg) was ineffective for the treatment of serotonin- and bradykinin-induced rat paw edema. When injected via the i.pl. route, CcL (10 mg/kg) elicited rat paw edema involving a wide range of mediators. CONCLUSIONS: The anti-inflammatory action of CcL involves the inhibition of IL-1ß, TNF-α, IL-6 and COX-2 expression and histamine H1 receptors. When locally administered, CcL exerts pro-inflammatory actions.

Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats.

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-1ß, 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.

Sulfated polysaccharides isolated from the green seaweed Caulerpa racemosa plays antinociceptive and anti-inflammatory activities in a way dependent on HO-1 pathway activation.

OBJECTIVE: Marine algae are abundant sources of sulfated polysaccharides with various biological activities. Consequently, their biomolecules are of great of commercial interest. In this study, we investigated the potential antinociceptive activity of a sulfated polysaccharide obtained from the green seaweed Caulerpa racemosa (CrII) and the involvement of the hemoxigenase-1 (HO-1) pathway in its anti-inflammatory effect. METHODS: We used a systemic evaluation to verify possible toxic effects of Crll after consecutive treatments. Swiss mice and Wistar rats were used for all experiments. RESULTS: In Swiss mice, CrII (0.01, 0.1 and 1.0 mg/kg) significantly reduced the number of abdominal contortions and the duration of paw licking in the second phase after treatment with acetic acid and formalin, respectively. However, CrII was unable to prolong the reaction time of thermally stimulated animals. The anti-inflammatory effect of CrII (0.01, 0.1 and 1.0 mg/kg) was evidenced by a decreased number of leukocytes in the peritoneal cavities of the rats. CrII (0.01, 0.1 and 1.0 mg/kg) also reduced the amount of paw edema induced by carrageenan (Cg) and dextran. The anti-inflammatory effect of CrII was confirmed by reduced levels of myeloperoxidase in the paw tissue of the Cg groups. After inhibition with ZnPP IX, a specific HO-1 phenotype inhibitor, the anti-inflammatory effect of CrII was no longer observed in Cg-induced paw edema tests. Consecutive Crll (1.0 mg/kg) for 14 days did not change any biochemical or histopathological parameters, or cause mortality of mice. CONCLUSIONS: CrII did not produce any signs of toxicity and effectively decreased nociception and inflammation. Also, the anti-inflammatory effect of Crll is at least in part dependent on the integrity of the HO-1 pathway.