Aloysia gratissima prevents cellular damage induced by glutamatergic excitotoxicity.
OBJECTIVE
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.


RESULTS
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.
Department of Biochemistry, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil; Department of Natural Sciences, Natural and Exact Sciences Center, Regional University of Blumenau, Blumenau, Santa Catarina, Brazil.
Ana L B
AL
Zeni
Samuel
S
Vandresen-Filho
Tharine
T
Dal-Cim
Wagner C
WC
Martins
Daniela B
DB
Bertoldo
Marcelo
M
Maraschin
Carla I
CI
Tasca
D000818:Animals; D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology / Q000627:therapeutic use; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D018846:Excitatory Amino Acids / Q000378:metabolism; D018698:Glutamic Acid / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017378:Quinolinic Acid / Q000009:adverse effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D029648:Verbenaceae / Q000737:chemistry*
D003373:Coumaric Acids; D018690:Excitatory Amino Acid Agonists; D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C004999:ferulic acid; D058539:Phosphatidylinositol 3-Kinase; D017378:Quinolinic Acid
Aloysia gratissima; cell viability; ferulic acid; neuroprotection; quinolinic acid