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.

Involvement of the dopaminergic system in the antidepressant-like effect of the lectin isolated from the red marine alga Solieria filiformis in mice.

This study aimed at evaluating the antidepressant-like action of the marine alga Solieria filiformis lectin (SfL) and to investigate the participation of the monoaminergic system in this action. For this, male Swiss mice (n=10) were pretreated with intravenous injections (i.v.) of SfL (1, 3 or 9mg/kg) and submitted to open field (OFT), tail suspension (TST), forced swimming (FST), elevated plus-maze (EPMT) and hole-board tests (HBT). As controls, mice received sterile saline (i.v.), imipramine (10 or 30mg/kg; intraperitoneally - i.p.) or diazepam (1 mk/kg; i.p.). To assess the involvement of the monoaminergic system in SfL effects, the FST was conducted in mice pretreated with PCPA, an inhibitor of serotonin synthesis, or noradrenergic and dopaminergic receptors specific antagonists. The results showed that SfL has an antidepressant-like effect, with no psychostimulant and anxiolytic-like effects. When denatured or combined with mannan, SfL lost the ability to reduce the immobility time in the FST. In addition, SfL antidepressant-like effect was inhibited by the pretreatment of mice with SCH 23390, a dopamine D1 receptor antagonist, and by sulpiride, a dopamine D2 receptor antagonist. Thus, SfL produced an antidepressant-like effect, which is probably dependent on its interaction with the dopaminergic system.

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.

A lectin from the green seaweed Caulerpa cupressoides reduces mechanical hyper-nociception and inflammation in the rat temporomandibular joint during zymosan-induced arthritis.

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-1ß 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-1ß inhibition. CcL reveals a potentially valuable alternative tool for future studies of TMJ disorders.