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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.

Depression and anxiety disorder are the most common mental disorders worldwide and their treatments are combinations of pharmacological and psychotherapeutic approaches. Depression treatment depends largely on a pharmacotherapy that improves the transmission of monoamines in the brain. However, the drugs available have adverse reactions and do not contemplate positively all patients, which stimulates scientific research that seeks new molecules, including from natural sources. Lectins are proteins capable of binding reversibly and non-covalently to specific sugars. For example, it has been reported the antimicrobial, antitumor, antiparasitic, anti-inflammatory and antinociceptive activities of lectins. The ability of some lectins in modulating nociception and inflammation stimulated studies on the possible effects on processes that share some pathways and molecular agents, like depression and anxiety. Lectins isolated from plants showed antidepressant effects, which were demonstrated to be linked to activation of serotonergic, adrenergic, and dopaminergic systems as well as to inhibition of the glutamatergic system and L-arginine–NO–cGMP pathway. In view of their immunomodulatory properties, it is also suggested that lectins can ameliorate the inflammatory framework associated with depression. Anxiolytic effects were also reported and associated with modulation of GABAergic mechanisms, serotonergic system, and NO pathway. It should be taken in account that some lectins induced depressive-like behavior, associated with an neuroinflammatory action, as well anxiogenic action. Thus, it is important to use combinations of batteries for testing anxiety, depression, despair, and anhedonia behaviors in the studies with lectins. The mechanisms by which lectins exactly modulate depression or anxiety frameworks are still unclear but important windows had already been open by researchers and preclinical studies with lectins have indicated these proteins as candidates for alternative or complementary agents in therapies of depression and anxiety disorder.