Efeito antidepressivo-símile da frutalina, lectina α-d-galactose ligante, isolada de sementes de Artocarpus incisa L., em camundongos

Abstract

Frutalin (FTL), an α-D-galactose-binding lectin isolated from breadfruit seeds (Artocarpus incisa L.), has a range biological activities, but has not been conclusively shown to act on CNS disorders. In this study we evaluated the effect of FTL on mouse behavior. Mice (n=6/group) were treated with FTL (0.25; 0.5 or 1 mg/kg; i.p.) or vehicle (NaCl 0.9 %;10 mL/kg; i.p.) and submitted to hole-board (HBT), elevated plus maze (PMT), open field (OFT), tail suspension (TST) and forced swimming (FST) tests. In a second set of experiments, yohimbine (1 mg/kg), ketamine (0.1 mg/kg), L-NAME (10 mg/kg) or methylene blue (10 mg/kg) were administered (i.p.) 30 min before FTL (0.5 mg/kg). In order to evaluate the subchronic effect of FTL, animals were injected with FTL (0.5 mg/kg) or vehicle for 7 days and submitted to FST on the first and last day of treatment. A molecular docking was conducted on the NOS enzyme and NMDA receptor. No changes were observed in HBT and OFT results. The smallest dose of FTL (0.25 mg/kg) was associated with an increase in the number of entries into closed arms in PMT (p<0.05). FTL reduced immobility in TST (0.25 and 0.5 mg/kg; p<0.05) and FST (0.25 mg/kg; p<0.05 and 0.5 mg/kg; p<0.01). In FST, the effect of FTL was dependent on carbohydrate interaction and protein structure integrity and it was reduced by ketamine (NMDA antagonist), L-NAME (non-selective NOS inhibitor) and methylene blue (soluble guanylyl cyclase inhibitor). The antidepressant-like effect remained after subchronic treatment. Matching the results of the experiment in vivo, the docking study indicated an interaction between FTL and NOS enzyme and NMDA receptor. In conclusion, FTL was found to have an antidepressant-like effect mediated by the NMDA receptor/NO/cGMP pathway.