Toxicity and antitumor activity of the water-soluble lectin from Moringa oleifera Lam. Seeds (WSMoL) in sarcoma 180-bearing mice.

WSMoL, a water-soluble lectin from the seeds of Moringa oleifera, present several biological activities. This work aimed to evaluated the toxicity and antitumor activity of WSMoL. To analyze toxicity, it was determined hematological, biochemical and histological parameters; consumption of water and feed as well as the weight of the animals. Antitumor analysis included evaluation of tumor weight, histology and cytokine levels. Acute toxicity assay revealed 60% mortality of animals treated with lectin at 200 mg/kg i. p. At 100 mg/kg i. p., the animals showed a decreased food and water consumption as well weight gain in comparison with control. However, no animal died and there were no alterations in blood parameters or histological analysis. Antitumor activity evaluated at safe doses (2.5, 5 and 10 mg/kg) showed a significant reduction in tumor weight. Tumor photomicrographs evidenced that WSMoL treatment reduced dissemination of tumor cells. WSMoL (5 and 10 mg/kg) significantly enhance the immune function in the tumor environment as showed by increased the levels of pro-inflammatory (TNF-α, IFN-γ, IL-2, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines. In conclusion, WSMoL showed in vivo antitumor activity in mice bearing sarcoma 180 tumor, probably by increase the immune response against the tumor.

Schinus terebinthifolia leaf lectin has central and peripheral antinociceptive action mediated by its carbohydrate-recognition domain and delta-opioid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations from the bark and leaves of Schinus terebinthifolia Raddi are commonly used to treat toothaches and sore throats. The use of medications based on leaves of this plant has also been reported for pain of arthritis, toothache, and sore throat. Some evidence indicated that the lectin SteLL is an antinociceptive agent from leaves. AIM OF THE STUDY: This study evaluated the antinociceptive activity of S. terebinthifolia leaf lectin (SteLL) using mouse models of peripheral and central nociception. MATERIALS AND METHODS: Animals were treated intraperitoneally with SteLL at 1, 5, and 10 mg/kg. An acetic acid-induced abdominal writhing test was performed to screen for the antinociceptive effect of the lectin. Next, the formalin test was used to assess the effects of SteLL on neurogenic (first phase) and inflammatory (second phase) pain, as well as to investigate the involvement of the carbohydrate-recognition domain (CRD) of SteLL and opioid receptors in the antinociceptive effect. The tail immersion test was performed to assess the central antinociception. Additionally, a rotarod test was performed to evaluate the effects of lectin on motor coordination in mice. RESULTS: SteLL reduced the number of acetic acid-induced writhes by 83.5-100.0%. In the first phase of the formalin test, SteLL reduced paw licking time by 49.4-50.5%, while in the second phase, SteLL reduced paw licking time by 80.5-82.6%. This antinociceptive effect was reversed by the previous incubation of the lectin with ovalbumin (indicating the possible involvement of the CRD) and by the administration of naloxone, a nonselective opioid receptor antagonist. When testing selective antagonists of opioid receptors (µ, δ, and κ), only naltrindole, a selective δ receptor antagonist, blocked the antinociceptive action of SteLL during the second phase of the formalin test. In the tail immersion test, SteLL (1, 5, and 10 mg/kg) administration reduced sensitivity to thermal stimulus, which was observed even after 2 h. SteLL (10 mg/kg) did not affect animal motor coordination in rotarod test when compared to the control group. CONCLUSION: SteLL has peripheral and central analgesic action involving opioid receptor modulation without affecting the motor coordination of animals. These results provide new perspectives for developing analgesic agents using lectins.

The Anxiolytic Activity of Schinus terebinthifolia Leaf Lectin (SteLL) Is Dependent on Monoaminergic Signaling although Independent of the Carbohydrate-Binding Domain of the Lectin.

The potential of plant lectins (carbohydrate-binding proteins) for the treatment of neurological disorders such as anxiety and depression has started to be reported in the last few years. Schinus terebinthifolia leaves contain a lectin called SteLL, which has displayed antimicrobial, immunomodulatory, antitumor, and analgesic activities. However, the effects of SteLL on the Central Nervous System (CNS) have not yet been determined. In this study, we investigated the in vivo anxiolytic effect of SteLL in mice using the open field (OF) and elevated plus maze (EPM) tests. In the OF, SteLL (1, 2, and 4 mg/kg, i.p.) did not interfere with the number of crossings but significantly reduced the number of rearings. In the EPM, SteLL 4 mg/kg and the combination SteLL (1 mg/kg) plus diazepam (1 mg/kg) significantly increased the time spent in the open arms while reducing the time spent in the closed arms. The anxiolytic effect of SteLL did not seem to be dependent on the carbohydrate-binding domain of the lectin. Nevertheless, the SteLL effect in the EPM was reversed by the pretreatment with the pharmacological antagonists of the α2-adrenoceptor, 5-HT2A/2C serotonin receptor, and the D1 dopamine receptor. Overall, our results suggest that the anxiolytic effect of SteLL is dependent on the monoaminergic signaling cascade.