Antidepressant-like and neuroprotective effects of Aloysia gratissima: Investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway

Ethnopharmacological relevance: Aloysia gratissima (Gill. et Hook) Tronc. (Verbenaceae) is used traditionally for the treatment of headache, bronchitis, and nervous systems disorders including depression. Aim of the study: To investigate the antidepressant-like and neuroprotective effects of Aloysia gratissima aqueous extract (AE) and the involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Materials and methods: The antidepressant-like effect of AE was evaluated through behavioral despair in forced swimming test (FST) and tail suspension test (TST). Swiss albino mice were treated by oral route and after 1 h were analyzed the time of immobility in the FST and TST. In addition, the neuroprotective effect of AE against glutamate excitotoxicity was evaluate through cell viability of hippocampal slices, phosphorylation of Akt, and the immunocontent of inducible oxide nitric synthase (iNOS) were investigated by western blotting. Results: The immobility time in the FST and TST were reduced by AE (100-1000 and 10-300 mg/kg, respectively). The antidepressant-like effect of AE in the TST was prevented by the pretreatment with N-methyl-D-aspartate (NMDA), L-arginine or sildenafil. The subeffective dose of AE produced a synergistic antidepressant-like effect with MK-801 (an antagonist of NMDA receptor), methylene blue, L-NNA (an inhibitor of NO synthase) or ODQ (an inhibitor of soluble guanylate cyclase). In ex vivo experiments, pretreatment with AE prevented the loss of cell viability induced by glutamate, thus affording neuroprotection. Glutamate toxicity caused a decreased Akt phosphorylation and an increased iNOS expression. Conclusions: The present study provides convincing evidence of neuroprotection and the involvement of the L-arginine-NO-cGMP pathway in the antidepressant-like effect of AE. Therefore, AE could be of potential interest for the treatment of depressive disorders and neurological conditions associated with glutamate excitotoxicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.