Antiulcer and Antioxidant Activity of a Lectin from Mucuna pruriens Seeds on Ethanol- induced Gastropathy: Involvement of Alpha-2 Adrenoceptors and Prostaglandins.

ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens (Mp) belongs to Leguminosae family, it is native of tropical regions and used to treat several maladies such as urinary, neurological, and menstruation disorders, constipation, edema, fever, tuberculosis, ulcers, diabetes, arthritis, dysentery, and cardiovascular diseases. Mp seeds are rich in bioactive compounds, for instance, lectins, a heterogeneous group of proteins and glycoproteins with a potential role as therapeutic tools for several conditions, including gastric disorders. This study investigated the acute toxicity, gastroprotective, and antioxidant activities of a lectin from Mucuna pruriens seeds (MpLec) on ethanol-induced gastropathy model in mice. MATERIAL AND METHODS: Mice received MpLec (5 or 10 mg/kg; i.v.) and were observed for acute toxicity signs; in another experimental series, mice were pre-treated with MpLec (0.001; 0.01 or 0.1 mg/kg, i.v.), ranitidine (80 mg/kg, p.o.), or saline (0.3 mL/30g, i.v.) before ethanol 99.9% (0.2 mL/animal, p.o.), and euthanized 30 min after ethanol challenge. Macroscopic and microscopic gastric aspects, biochemical parameters (tissue hemoglobin levels, iron-induced lipid peroxidation, GSH content, SOD activity, and gastric mucosal PGE2) were measured. Additionally, pharmacological tools (yohimbine, indomethacin, naloxone, L-NAME) were opportunely used to clarify MpLec gastroprotective mechanisms of action. RESULTS: No toxicity signs nor death were observed at acute toxicity tests. MpLec reduced ethanol-induced gastric damage, edema, and hemorrhagic patches formation, as well as decreased lipid peroxidation, SOD activity, and increased GSH content. Yohimbine and indomethacin prevented MpLec effects, suggesting the involvement of alpha-2 adrenoceptors and prostaglandins in the MpLec-mediated effects. CONCLUSION: MpLec does not present toxicity signs and shows gastroprotective and antioxidant activities via alpha-2 adrenoceptors and prostaglandins in the ethanol-induced gastropathy model.

The efficacy of a lectin from Abelmoschus Esculentus depends on central opioid receptor activation to reduce temporomandibular joint hypernociception in rats.

Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, e.g. inflammatory conditions. This study aimed to evaluate the efficacy of Abelmoschus esculentus lectin (AEL) in reducing formalin-induced temporomandibular joint inflammatory hypernociception in rats. The behavioral experiments were performed in male Wistar rats (180-240 g). Rats were pre-treated (i.v.) with AEL (0.001, 0.01 or 0.1 mg/kg) 30 min before formalin injection (i.art.). To analyze the possible effect of opioid pathways on AEL efficacy, animals were pre-treated with naloxone or CTOP (µ opioid receptor antagonist), naltrindole (δ opioid receptor antagonist) or nor-binaltorphimine (κ opioid receptor antagonist) (i.t.) 15 min before AEL administration followed by intra-TMJ injection of 1.5% formalin. Animals were monitored for a 45-min observation period. TMJ tissue, trigeminal ganglion, and subnucleus caudalis were collected for TNF-α dosage (ELISA). In addition, the vascular permeability was evaluated by Evans Blue extravasation. AEL significantly reduced formalin-induced TMJ inflammatory hypernociception and decreased Evans blue extravasation. It decreased TNF-α levels in the TMJ tissue, trigeminal ganglion, and subnucleus caudalis. AEL antinociceptive effects were not observed in the presence of naltrindole or nor-binaltorphimine, suggesting that AEL efficacy depends on TNF-α inhibition and the activation of δ and κ opioid receptors. AEL has provided prominent analgesic and anti-inflammatory effects in this pre-clinical model of TMJ, supporting its possible use as a pharmacological tool for the management of painful conditions.

Anti-inflammatory and anti-nociceptive effects of strontium ranelate on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats depend on TNF-α inhibition.

BACKGROUND: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Strontium ranelate has previously shown anti-inflammatory and antinociceptive effects on other experimental inflammatory pain models. Thus, we aim to investigate the strontium ranelate efficacy in reducing the zymosan-induced inflammatory hypernociception in the TMJ of rats by evaluating the TNF-α, IL-1ß, and hemeoxygenase-1 (HO-1) involvement. METHODS: Wistar rats were treated with strontium ranelate (0.5, 5 or 50 mg/kg, per os) 1 h before zymosan injection (iart). Mechanical threshold was assessed by Von Frey test and synovial lavage was collected for leukocyte counting and myeloperoxidase measurement, joint tissue and trigeminal ganglion were excised for histopathological analysis (H&E) and TNF-α/IL-1ß levels dosage (ELISA). Moreover, rats were pre-treated with ZnPP-IX (3 mg/kg, sc), a specific HO-1 inhibitor, before strontium ranelate administration (0.5 mg/kg, per os), and Evans Blue (5 mg/kg, iv) was administered to assess plasma extravasation. Pre-treatment with indomethacin (5 mg/kg, sc) was used as positive control while the sham group received 0.9% sterile saline (per os and iart). RESULTS: Strontium ranelate did not reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1ß levels, and TNF-α/IL-1ß immunolabeling; but it increased the nociceptive threshold and reduced TNF-α levels. Additionally, HO-1 inhibition did not change the strontium ranelate effects. CONCLUSION: Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1ß expression nor inducing the HO-1 pathway.

Role of central opioid on the antinociceptive effect of sulfated polysaccharide from the red seaweed Solieria filiformis in induced temporomandibular joint pain.

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225µg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or µ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the ß-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.

Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1ß suppression.

Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1ß, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1ß dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1ß expression in the TMJ tissue. AEL reduced TNF-α and IL-1ß levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1ß inhibition and HO-1 pathway integrity.