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

Abstract

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.

Keywords: anxiety; elevated plus maze; lectin; mice models; open field.

Figure 1

Effects of SteLL (1, 2, and 4 mg/kg) i.p. treatment in the open field test. Diazepam (1 mg/kg) was used as a positive control. Diazepam (0.5 mg/kg) plus SteLL (1 mg/kg) was used to evaluate the synergic effect of both compounds combined. (a) Total number of crossings. (b) Total number of rearings. (c) Frequency of the mice entering the center zone. (d) The overall duration of time mice spent in the center of the apparatus. Significant differences compared with the control group: (*) p < 0.05; (**) p < 0.001; (***) p < 0.0001; (****) p < 0.00001.

Figure 2

Effects of SteLL (1, 2, and 4 mg/kg) i.p. treatment on the elevated plus maze test. Diazepam (1 mg/kg) was used as a positive control. Diazepam (0.5 mg/kg) plus SteLL (1 mg/kg) was used to evaluate the synergic effect of both compounds combined. (a) Total time that mice spent in open arms. (b) The number of entries into the open arms. (c) Total time spent in closed arms. (d) The number of entries into the closed arms. Significant differences compared with the control group: (*) p < 0.05; (**) p < 0.001; (***) p < 0.0001; (****) p < 0.00001.

Figure 3

The incubation of the lectin with casein did not revert the anxiolytic effect of SteLL (4 mg/kg) in the elevated plus maze test. (a) Total time that mice spent in open arms. (b) The number of entries into the open arms. (c) Total time spent in closed arms. (d) The number of entries into the closed arms. (*) p < 0.05; (**) p < 0.001; (***) p < 0.0001 compared to control.

Figure 4

The incubation of the lectin with casein did not revert the anxiolytic effect of SteLL (4 mg/kg) in the open field test. (a) Total number of crossings. (b) Total number of rearings. (*) p < 0.05; (**) p < 0.001; (***) p < 0.0001 compared to control.

Figure 5

The anxiolytic-like effect of SteLL in the EPM was dependent on monoaminergic signaling. The pretreatment with the nonselective antagonist of the α2-adrenoceptor yohimbine 1 mg/kg, the 5-HT2A/2C serotonin receptor antagonist ketanserin 5 mg/kg, and the D1 dopamine receptor antagonist SCH 23390 0.05 mg/kg inhibited the effect of SteLL (4 mg/kg) on the time spent in the open (a) and closed (c) arms. No changes were observed in the number of entries in open (b) and closed (d) arms. The antagonists were administrated 15 min before SteLL administration. The experiments were conducted 15 min after SteLL administration. (**) p < 0.001; (***) p < 0.0001 compared to control.

Figure 6

The blockage of the monoaminergic signaling did not alter the rearing responses of SteLL administration (4 mg/kg) on the OFT. The nonselective antagonist of the α2-adrenoceptor yohimbine 1 mg/kg, the 5-HT2A/2C serotonin receptor antagonist ketanserin 5 mg/kg, and the D1 dopamine receptor antagonist SCH 23390 0.05 mg/kg were evaluated. (a) There were no significant changes in the numbers of crossing among the groups. (b) SteLL 4 mg/kg decreased the number of rearings compared to the control even in animals pretreated with the antagonists. (*) p < 0.05; (**) p < 0.001; (***) p < 0.0001 compared to control.