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Glioblastoma multiforme (GBM) is the most aggressive type of glioma, displaying atypical glycosylation pattern that may modulate signaling pathways involved in tumorigenesis. Lectins are glycan binding proteins with antitumor properties. The present study was designed to evaluate the antitumor capacity of the Dioclea reflexa lectin (DrfL) on glioma cell cultures. Our results demonstrated that DrfL induced morphological changes and cytotoxic effects in glioma cell cultures of C6, U-87MG and GBM1 cell lines. The action of DrfL was dependent upon interaction with glycans, and required a carbohydrate recognition domain (CRD), and the cytotoxic effect was apparently selective for tumor cells, not altering viability and morphology of primary astrocytes. DrfL inhibited tumor cell migration, adhesion, proliferation and survival, and these effects were accompanied by activation of p38 MAPK and JNK (p46/54), along with inhibition of Akt and ERK1/2. DrfL also upregulated pro-apoptotic (BNIP3 and PUMA) and autophagic proteins (Atg5 and LC3 cleavage) in GBM cells. Noteworthy, inhibition of autophagy and caspase-8 were both able to attenuate cell death in GBM cells treated with DrfL. Our results indicate that DrfL cytotoxicity against GBM involves modulation of cell pathways, including MAPKs and Akt, which are associated with autophagy and caspase-8 dependent cell death., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects.

The mTORC1-dependent dendritic spines formation represents a key mechanism for fast and long-lasting antidepressant responses, but it remains to be determined whether this mechanism may account for the ability of guanosine in potentiating ketamine's actions. Here, we investigated the ability of ketamine plus guanosine to elicit fast and sustained antidepressant-like and pro-synaptogenic effects in mice and the role of mTORC1 signaling in these responses. The combined administration of subthreshold doses of ketamine (0.1 mg/kg, i.p.) and guanosine (0.01 mg/kg, p.o.) caused a fast (1 h - 24 h), but not long-lasting (7 days) reduction in the immobility time in the tail suspension test. This behavioral effect was paralleled by a rapid (started in 1 h) and transient (back to baseline in 24 h) increase on BDNF, p-Akt (Ser 473 ), p-GSK-3β (Ser 9 ), p-mTORC1 (Ser 2448 ), p-p70S6K (Thr 389 ) immunocontent in the hippocampus, but not in the prefrontal cortex. Conversely, ketamine plus guanosine increased PSD-95 and GluA1 immunocontent in the prefrontal cortex, but not the hippocampus after 1 h, whereas increased levels of these proteins in both brain structures were observed after 24 h, but these effects did not persist after 7 days. The combined administration of ketamine plus guanosine raised the dendritic spines density in the ventral hippocampal DG and prefrontal cortex after 24 h Rapamycin (0.2 nmol/site, i.c.v.) abrogated the antidepressant-like effect and pro-synaptogenic responses triggered by ketamine plus guanosine. These results indicate that guanosine may boost the antidepressant-like effect of ketamine for up to 24 h by a mTORC1-dependent mechanism., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier B.V. and ECNP. All rights reserved.)

Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant whose mechanisms of action involve oxidation of endogenous nucleophilic groups (mainly thiols and selenols), depletion of antioxidant defenses, and disruption of neurotransmitter homeostasis. Diphenyl diselenide-(PhSe) 2 -a model diaryl diselenide, has been reported to display significant protective effects against MeHg-induced neurotoxicity under both in vitro and in vivo experimental conditions. In this study, we compared the protective effects of (PhSe) 2 with those of RC513 (4,4'-diselanediylbis(2,6-di-tert-butylphenol), a novel diselenide-probucol-analog) against MeHg-induced toxicity in the neuronal (hippocampal) cell line HT22. Although both (PhSe) 2 and RC513 significantly mitigated MeHg- and tert-butylhydroperoxide (t-BuOOH)-cytotoxicity, the probucol analog exhibited superior protective effects, which were observed earlier and at lower concentrations compared to (PhSe) 2 . RC513 treatment (at either 0.5 µM or 2 µM) significantly increased glutathione peroxidase (GPx) activity, which has been reported to counteract MeHg-toxicity. (PhSe) 2 was also able to increase GPx activity, but only at 2 µM. Although both compounds increased the Gpx1 transcripts at 6 h after treatments, only RC513 was able to increase mRNA levels of Prx2, Prx3, Prx5, and Txn2, which are also involved in peroxide detoxification. RC513 (at 2 µM) significantly increased GPx-1 protein expression in HT22 cells, although (PhSe) 2 displayed a minor (nonsignificant) effect in this parameter. In agreement, RC513 induced a faster and superior capability to cope with exogenously-added peroxide (t-BuOOH). In summary, when compared to the prototypical organic diaryl diselenide [(PhSe) 2 ], RC513 displayed superior protective properties against MeHg-toxicity in vitro; this was paralleled by a more pronounced upregulation of defenses related to detoxification of peroxides, which are well-known MeHg-derived intermediate oxidant species., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ketamine exhibits rapid and sustained antidepressant responses, but its repeated use may cause adverse effects. Augmentation strategies have been postulated to be useful for the management/reduction of ketamine's dose and its adverse effects. Based on the studies that have suggested that ketamine and guanosine may share overlapping mechanisms of action, the present study investigated the antidepressant-like effect of subthreshold doses of ketamine and guanosine in mice subjected to repeated administration of corticosterone (CORT) and the role of mTORC1 signaling for this effect. The ability of the treatment with ketamine (0.1 mg/kg, i.p.) plus guanosine (0.01 mg/kg, p.o.) to counteract the depressive-like behavior induced by CORT (20 mg/kg, p.o., for 21 days) in mice, was paralleled with the prevention of the CORT-induced reduction on BDNF levels, Akt (Ser 473 ) and GSK-3β (Ser 9 ) phosphorylation, and PSD-95, GluA1, and synapsin immunocontent in the hippocampus. No changes on mTORC1 and p70S6K immunocontent were found in the hippocampus and prefrontal cortex of any experimental group. No alterations on BDNF, Akt/GSK-3β, mTORC1/p70S6K, and synaptic proteins were observed in the prefrontal cortex of mice. The antidepressant-like and pro-synaptogenic effects elicited by ketamine plus guanosine were abolished by the pretreatment with rapamycin (0.2 nmol/site, i.c.v., a selective mTORC1 inhibitor). Our results showed that the combined administration of ketamine and guanosine at low doses counteracted CORT-induced depressive-like behavior and synaptogenic disturbances by activating mTORC1 signaling. This study supports the notion that the combined administration of guanosine and ketamine may be a useful therapeutic strategy for the management of MDD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ketamine has emerged as a prophylactic agent against depressive-like behavior induced by stress. However, the possible pro-resilience effects of ketamine against inflammatory stressors-induced depressive-like behavior and the signaling pathways associated with this response remain to be determined. Therefore, this study investigated the ability of prophylactic ketamine administration to produce a pro-resilience effect against the depressive-like behavior induced by lipopolysaccharide (LPS - 0.83 mg/kg, i.p.) and tumor necrosis factor-alpha (TNF-α - 0.1 fg/site, i.c.v.) administration in mice. The possible contribution of the NLRP3 inflammasome-driven signaling pathway to this effect was evaluated in the ventral hippocampus. A single administration of ketamine (5 mg/kg, i.p.) given 1 week before the LPS or TNF-α administration prevented the depressive-like behavior induced by these inflammatory stressors in the tail suspension test (TST) and splash test (SPT). On the other hand, a lower dose of ketamine (1 mg/kg, i.p.) failed to produce a similar effect. The administration of LPS, but not TNF-α, increased the immunocontent of the microglial marker Iba-1 in the ventral hippocampus. LPS increased the immunocontent of all proteins related to NLRP3 signaling, namely ASC, NLRP3, TXNIP, cleaved caspase-1, and IL-1β in this brain region, while TNF-α only increased ASC and NLRP3 immunocontent. Ketamine administered at the dose of 5 mg/kg, but not at 1 mg/kg, prevented the increase on the immunocontent of NLRP3 inflammasome complex components and regulators induced by LPS or TNF-α administration. Collectively, these findings suggest that ketamine elicits a pro-resilient phenotype against inflammatory stressors-induced depressive-like behavior, an effect associated with the suppression of the NLRP3 inflammasome-driven signaling pathway., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Fluoxetine is the foremost prescribed antidepressant. Drugs acting on monoaminergic system may also regulate glutamatergic system. Indeed, the investigation of proteins associated with this system, such as Narp (neuronal activity-dependent pentraxin) and GluA4 subunit of AMPA receptor may reveal poorly explored modulations triggered by conventional antidepressants. This study aimed to uncover neurochemical mechanisms underlying the chronic fluoxetine treatment, mainly by evaluating these protein targets in the prefrontal cortex and in the hippocampus. Mice received a daily administration of fluoxetine (0.1, 1 or 10 mg/kg, p.o.) or potable water (vehicle group) for 21 days. These animals were submitted to the forced swim test (FST) to verify antidepressant-like responses and the open-field test (OFT) to assess locomotor activity. Modulation of signaling proteins was analyzed by western blot. Chronic treatment with fluoxetine (1 and 10 mg/kg) was effective, since it reduced the immobility time in the FST, without altering locomotor activity. Fluoxetine 10 mg/kg increased CREB phosphorylation and BDNF expression in the prefrontal cortex and hippocampus. Noteworthy, in the hippocampus fluoxetine also promoted Akt activation and augmented Narp expression. In the prefrontal cortex, a significant decrease in the expression of the GluA4 subunit and Narp were observed following fluoxetine administration (10 mg/kg). The results provide evidence of novel molecular targets potentially involved in the antidepressant effects of fluoxetine, since in mature rodents Narp and GluA4 are mainly expressed in the GABAergic parvalbumin-positive (PV+) interneurons. This may bring new insights into the molecular elements involved in the mechanisms underlying the antidepressant effects of fluoxetine.

Amyloid beta (Aβ), one of the main hallmarks of Alzheimer's Disease (AD), may stimulate pattern recognition receptors (PRR) such as the NLRP3 inflammasome, inducing a pro-inflammatory state in the brain that contributes to disease development. Physical exercise can have multiple beneficial effects on brain function, including anti-inflammatory and neuroprotective roles. The objective of this study was to investigate the prophylactic effect of moderate treadmill exercise for 4 weeks on inflammatory events related to NLRP3 signaling in the hippocampus of mice after intracerebroventricular Aβ 1-40 administration. Our results show that Aβ 1-40 administration (400 pmol/mouse, i.c.v.) significantly increased the immunocontent Iba-1 (a microglial reactivity marker), NLRP3, TXNIP, and caspase-1 in the hippocampus of mice. However, physical exercise prevented the hippocampal increase in Iba-1, TXNIP, and activation of the NLRP3 inflammasome pathway caused by Aβ 1-40 . Moreover, physical exercise per se reduced the TXNIP and caspase-1 immunocontent in the hippocampus. No alterations were observed on the immunocontent of GFAP, ASC, and IL-1β in the hippocampus after Aβ 1-40 and/or physical exercise. These results reinforce the role of NLRP3 inflammasome pathway in AD and point to physical exercise as a possible non-pharmacological strategy to prevent inflammatory events triggered by Aβ 1-40 in mice.

Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38 MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Alzheimer's disease (AD) is a prevalent neurodegenerative disease that is highly comorbid with depression. Gut dysfunction has been proposed as a possible risk factor for both clinical conditions. In the present study, we investigated the ability of treadmill exercise for 4 weeks (5 days/week, 40 min/day) to counteract amyloid β 1-40 peptide (Aβ 1-40 )-induced depressive-like behavior, alterations in morphological parameters of the duodenum, and the abundance of Firmicutes and Bacteroidetes phyla. Aβ 1-40 administration (400 pmol/mouse, i.c.v.) increased immobility time in the tail suspension test (TST) and reduced time spent sniffing in the female urine sniffing test (FUST), indicating behavioral despair and impairment in reward-seeking behavior. These behavioral alterations, indicative of depressive-like behavior, were accompanied by reduced villus width in the duodenum. Moreover, photomicrographs obtained by transmission electron microscopy revealed abnormal epithelial microvilli in the duodenum from sedentary Aβ 1-40 -exposed mice, characterized by shorter microvilli and heterogeneity in the length of these structures that exhibit a disordered packing. Regarding the ultrastructure of Paneth cells, Aβ 1-40 administration caused a reduction in the secretory granule diameter, as well as an enlarged peripheral halo. These animals also presented reduced Firmicutes and increased Bacteroidetes abundance, and increased Bacteroidetes/Firmicutes ratio. Most of the alterations observed in Aβ 1-40 -exposed mice were prevented by the practice of physical exercise. Altogether the results provide evidence of the prophylactic effect of physical exercise on Aβ 1-40 -induced depressive-like behavior and gut dysfunction in mice, suggesting that physical exercise could be useful for preventing depression associated with AD., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lectins from Diocleinae subtribe species (family Leguminosae) are of special interest since they present a wide spectrum of biological activities, despite their high structural similarity. During their synthesis in plant cells, these proteins undergo post-translational processing resulting in the formation of three chains (α, β, γ), which constitute the lectins' subunits. Furthermore, such wild-type proteins are presented as isolectins or with different combinations of these chains, which undermine their biotechnological potential. Thus, the present study aimed to produce a recombinant form of the lectin from Dioclea sclerocarpa seeds (DSL), exclusively constituted by α-chain. The recombinant DSL (rDSL) was successfully expressed in E. coli BL21 (DE3) and purified by affinity chromatography (Sephadex G-50), showing a final yield of 74 mg of protein per liter of culture medium and specificity for D-mannose, α-methyl-mannoside and melibiose, unlike the wild-type protein. rDSL presented an effective vasorelaxant effect in rat aortas up to 100% and also interacted with glioma cells C6 and U87. Our results demonstrated an efficient recombinant production of rDSL in a bacterial system that retained some biochemical properties of the wild-type protein, showing wider versatility in sugar specificities and better efficacy in its activity in the biological models evaluated in this work., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The ketamine's potential for the treatment of refractory depression and anxiety has been considered one the most important discoveries in the last years, however, repeated use of ketamine is limited due to its side/adverse effects. Therefore, the search for effective augmentation strategies that may reduce ketamine doses is welcome. Therefore, this study sought to augment the effect of ketamine by guanosine in the novelty-suppressed feeding (NSF) test, a behavioral paradigm able to detect depression/anxiety-related behavior. Acute administration of guanosine (0.05 mg/kg, p.o.), similar to ketamine (1 mg/kg, i.p.), produced a rapid behavioral response in mice submitted to NSF test. Moreover, the coadministration of sub-effective doses of guanosine (0.01 mg/kg, p.o.) and ketamine (0.1 mg/kg, i.p.) was effective in mice submitted to NSF test. Subsequently, the intracellular mechanism underpinning the augmentation effect of ketamine by guanosine was investigated. Our results suggest that augmentation response of ketamine by guanosine in the NSF test probably involves the activation of mTOR signaling, since the treatment with rapamycin (0.2 nmol/site, i.c.v., a selective mTOR inhibitor) completely abolished this effect. This augmentation strategy also increased mTOR phosphorylation (Ser 2448 ) in the hippocampus, reinforcing the role of mTOR in this augmentation response. However, no changes in the p70S6K, PSD-95, GluA1, and synapsin immunocontents were found in the hippocampus of ketamine plus guanosine-treated mice. Overall, results provide evidence that guanosine is able to augment the effect of ketamine in the NSF test via mTOR activation, a finding that might have therapeutic implications for the management of depression/anxiety., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The antitumor activity of DVL, a lectin purified from Dioclea violacea seeds, on the U87 human glioma cell line was evaluated and compared with Canavalia ensiformis lectin (ConA). Treatment with DVL (10-100 μg/mL; 24-96 h) induced alterations in cell morphology, decreased cell numbers and clonogenic survival in a time- and concentration-dependent manner. DVL caused significant decreases in cell viability and impaired cell migration. Mechanistically, DVL treatment (12 h) disrupted mitochondrial electrochemical gradient, without ROS accumulation or caspase activation. In the absence of apoptosis, DVL (30-100 μg/mL), instead, induced autophagy, as detected by acridine orange staining and cleavage of LC3I. Inhibition of autophagy with 3-Methyladenine (3-MA) and Chloroquine partially abrogated DVL, but not ConA, cytotoxicity. The modulation of signaling pathways that orchestrate autophagic and cell survival processes were analyzed. DVL (30-100 μg/mL) decreased Akt, mTORC1 and ERK1/2 phosphorylation and augmented JNK(p54) and p38 MAPK phosphorylation. DVL was more potent than ConA for most parameters analyzed. Even though both lectins showed cytotoxicity to glioma cells, they spared primary astrocyte cultures. The results suggest a selective antiglioma activity of DVL by inhibiting U87 glioma cell migration and proliferation and inducing cell death, partially associated with autophagy, and likely involving Akt and mTORC1 dephosphorylation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most robust neurobiological findings in the pathophysiology of major depressive disorder (MDD) over the last 40 years. The persistent increase in glucocorticoids levels induces morphological and anatomical changes in the brain, especially in the hippocampus. Ketamine represents a major advance for the treatment of MDD, however the psychotomimetic effects of this compound limit its widespread use. Agmatine is a neuromodulator that has been shown to be a putative novel and well-tolerated antidepressant/augmenter drug. In this study, the exposure of HT22 hippocampal neuronal cell line to corticosterone (50 μM) induced a significant neuronal cell death. Interestingly, the incubation of HT22 cells with the fast-acting antidepressant drug ketamine (1 μM) prevented the corticosterone-induced toxicity. Similarly, agmatine caused a significant cytoprotection at the concentration of 0.1 μM against corticosterone (50 μM) cell damage. Notably, the incubation with a subthreshold concentration of ketamine (0.01 μM) in combination with a subthreshold concentration of agmatine (0.001 μM) prevented the neuronal damage elicited by corticosterone (50 μM). A 24 h co-incubation with subthreshold concentrations of ketamine (0.01 μM) and agmatine (0.001 μM) was able to cause a significant increase in the phosphorylation levels of Akt (Ser 473 ) and p70S6 kinase (Thr 389 ) as well as PSD95 immunocontent. Neither glycogen synthase kinase-3β (Ser 9 ) phosphorylation nor β catenin immunocontent were altered by a 24 h co-incubation period. Finally, the co-incubation of cells for 30 min did not produce any effect in the phosphorylation or immunocontent of any protein investigated. Taken together, our results support the notion that the combination of subthreshold concentrations of ketamine and agmatine has cytoprotective effects against corticosterone-induced cell death. This effect is accompanied by its ability to activate Akt and mTOR/S6 kinase signaling pathway, and increase the expression of synaptic proteins., (Copyright © 2018. Published by Elsevier Ltd.)

CaBo is a mannose/glucose-specific lectin purified from seeds of Canavalia bonariensis. In the present work, we report the CaBo crystal structure determined to atomic resolution in the presence of X-man, a specific ligand. Similar to the structural characteristics of other legume lectins, CaBo presented the jellyroll motif, a metal binding site occupied by calcium and manganese ions close to the carbohydrate-recognition domain (CRD). In vitro test of CaBo cytotoxicity against glioma cells demonstrated its ability to decrease the cellular viability and migration by induction of autophagy and cell death. Molecular docking simulations corroborate previous data indicating that the lectin's biological activities occur mostly through interactions with glycoproteins since the lectin interacted favorably with several N-glycans, especially those of the high-mannose type. Together, these results suggest that CaBo interacts with glycosylated cell targets and elicits a remarkable antiglioma activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Lectins are multidomain proteins that specifically recognize various carbohydrates. The structural characterization of these molecules is crucial in understanding their function and activity in systems and organisms. Most cancer cells exhibit changes in glycosylation patterns, and lectins may be able to recognize these changes. In this work, Dioclea lasiocarpa seed lectin (DLL) was structurally characterized. The lectin presented a high degree of similarity with other lectins isolated from legumes, presenting a jelly roll motif and a metal-binding site stabilizing the carbohydrate-recognition domain. DLL demonstrated differential interactions with carbohydrates, depending on type of glycosidic linkage present in ligands. As observed by the reduction of cell viability in C6 cells, DLL showed strong antiglioma activity by mechanisms involving activation of caspase 3., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A lectin from Canavalia virosa, Diocleinae subtribe, was purified by affinity chromatography with Sephadex G-50 matrix and named ConV. The primary structure of ConV was obtained by mass spectrometry and crystals were obtained by the vapor diffusion method at 293K and belonged to orthorhombic space group P2 1 22 1 with two molecules in its asymmetric unit. The structure obtained presented R factor and R free of 18.91% and 24.92% respectively, with no residues in nonallowed regions of Ramachandran plot. The crystal structure was solved at 2.53Å and was demonstrated to be very similar to other lectins from the same subtribe. In inflammatory tests, ConV elicited paw edema, but incubation of lectin with glucose beforehand was able to reduce the edematogenic effect, indicating the involvement of the carbohydrate recognition domain in this process. The lectin also showed toxicity to rat C6 glioma cells, disrupting the mitochondrial membrane potential (ΔYm) and decreasing cell viability, indicating an anticancer potential for ConV. In silico studies confirmed that ConV interacts strongly with carbohydrates that comprise the N-glycans of glycoproteins. This finding corroborates the hypothesis which holds that the lectin domain interacts with glycans in molecular targets and that this contributes to the effects observed in biological activities., (Copyright © 2016 Elsevier B.V. All rights reserved.)