Aloysia gratissima prevents cellular damage induced by glutamatergic excitotoxicity.

Abstract

OBJECTIVES:

Aloysia gratissima aqueous extract (AE) was investigated as a putative protective agent against quinolinic acid (QA)-induced seizures in mice and hippocampal cell damage. Additionally, AE and ferulic acid (FA), the major compound of AE, were tested against neurotoxicity evoked by glutamate or its N-methyl-D-aspartate receptor (NMDAR) agonist, QA on hippocampal slices, in vitro.

METHODS:

Mice were treated with AE before QA infusion (36.8 nmol/site) and seizures were analysed. Cellular viability and modulation of excitatory amino acid transport were verified in hippocampal slices. In-vitro AE or FA was tested against neurotoxicity induced by glutamate or QA.

KEY FINDINGS:

AE did not prevent QA-induced seizures; however, it prevented cellular death and disruption of excitatory amino acid transport. In-vitro AE (0.1 or 1.0 mg/ml) or FA (1 or 10 μm), improved cell viability against citotoxicity exerted by glutamate or QA, respectively. Both AE and FA have protective effects depending on activation of the phosphatidylinositol-3 kinase (PI3K) signalling pathway.

CONCLUSIONS:

AE attenuated QA-induced cell damage possibly involving the glutamate transport modulation through NMDAR interaction. FA shows a similar profile of neuroprotection promoted by AE. Therefore, AE treatment might be a useful strategy in preventing brain damage caused by exacerbation of glutamatergic toxicity in nervous system disorders.

• Authors: Ana L B Zeni, Samuel Vandresen-Filho, Tharine Dal-Cim, Wagner C Martins, Daniela B Bertoldo, Marcelo Maraschin, Carla I Tasca
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 66 Issue 9 Pg. 1294-302 (Sep 2014) ISSN: 2042-7158 [Electronic] England
• PMID: 24707860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Royal Pharmaceutical Society.

Chemical References

• Coumaric Acids
• Excitatory Amino Acid Agonists
• Excitatory Amino Acids
• Neuroprotective Agents
• Plant Extracts
• Receptors, N-Methyl-D-Aspartate
• Glutamic Acid
• ferulic acid
• Phosphatidylinositol 3-Kinase
• Quinolinic Acid

Topics

• Animals
• Biological Transport
• Cell Death (drug effects)
• Cell Survival (drug effects)
• Coumaric Acids (pharmacology, therapeutic use)
• Excitatory Amino Acid Agonists (adverse effects)
• Excitatory Amino Acids (metabolism)
• Glutamic Acid (adverse effects)
• Hippocampus (drug effects, metabolism, pathology)
• Male
• Mice, Inbred Strains
• Neuroprotective Agents (pharmacology, therapeutic use)
• Neurotoxicity Syndromes (drug therapy, metabolism, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Quinolinic Acid (adverse effects)
• Receptors, N-Methyl-D-Aspartate (agonists)
• Seizures (chemically induced, metabolism)
• Verbenaceae (chemistry)