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Aloysia gratissima prevents cellular damage induced by glutamatergic excitotoxicity.

AbstractOBJECTIVES:
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.
AuthorsAna L B Zeni, Samuel Vandresen-Filho, Tharine Dal-Cim, Wagner C Martins, Daniela B Bertoldo, Marcelo Maraschin, Carla I Tasca
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 66 Issue 9 Pg. 1294-302 (Sep 2014) ISSN: 2042-7158 [Electronic] England
PMID24707860 (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)

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