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J Pharm Pharmacol ; 66(9): 1294-302, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24707860

RESUMEN

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.


Asunto(s)
Ácido Glutámico/efectos adversos , Hipocampo/efectos de los fármacos , Síndromes de Neurotoxicidad/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Ácido Quinolínico/efectos adversos , Verbenaceae/química , Animales , Transporte Biológico , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/uso terapéutico , Agonistas de Aminoácidos Excitadores/efectos adversos , Aminoácidos Excitadores/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Ratones Endogámicos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Fosfatidilinositol 3-Quinasa/metabolismo , Extractos Vegetales/farmacología , Receptores de N-Metil-D-Aspartato/agonistas , Convulsiones/inducido químicamente , Convulsiones/metabolismo
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