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Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.
J Ethnopharmacol. 2011 Sep 01; 137(1):864-74.JE

Abstract

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 1h 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.

Authors+Show Affiliations

Biochemistry Department, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21767626

Citation

Zeni, Ana Lúcia Bertarello, et al. "Antidepressant-like and Neuroprotective Effects of Aloysia Gratissima: Investigation of Involvement of L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway." Journal of Ethnopharmacology, vol. 137, no. 1, 2011, pp. 864-74.
Zeni AL, Zomkowski AD, Dal-Cim T, et al. Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. J Ethnopharmacol. 2011;137(1):864-74.
Zeni, A. L., Zomkowski, A. D., Dal-Cim, T., Maraschin, M., Rodrigues, A. L., & Tasca, C. I. (2011). Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. Journal of Ethnopharmacology, 137(1), 864-74. https://doi.org/10.1016/j.jep.2011.07.009
Zeni AL, et al. Antidepressant-like and Neuroprotective Effects of Aloysia Gratissima: Investigation of Involvement of L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway. J Ethnopharmacol. 2011 Sep 1;137(1):864-74. PubMed PMID: 21767626.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway. AU - Zeni,Ana Lúcia Bertarello, AU - Zomkowski,Andréa Dias Elpo, AU - Dal-Cim,Tharine, AU - Maraschin,Marcelo, AU - Rodrigues,Ana Lúcia S, AU - Tasca,Carla I, Y1 - 2011/07/08/ PY - 2011/03/14/received PY - 2011/06/10/revised PY - 2011/07/03/accepted PY - 2011/7/20/entrez PY - 2011/7/20/pubmed PY - 2011/12/28/medline SP - 864 EP - 74 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 137 IS - 1 N2 - 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 1h 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/21767626/Antidepressant_like_and_neuroprotective_effects_of_Aloysia_gratissima:_investigation_of_involvement_of_L_arginine_nitric_oxide_cyclic_guanosine_monophosphate_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(11)00484-3 DB - PRIME DP - Unbound Medicine ER -