Restorative neurology and neuroscience · 2015
Involvement of the GABAergic system in the neuroprotective and sedative effects of acacetin 7-O-glucoside in rodents.
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Gálvez Javier, Estrada-Reyes Rosa, Benítez-King Gloria, Araujo Gabriela, Orozco Sandra, Fernández-Mas Rodrigo, Almazán Salvador, Calixto Eduardo
Аннотация
PURPOSE: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O-glucoside (7-ACAG).
METHODS: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis.
RESULTS: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus.
CONCLUSIONS: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.
METHODS: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis.
RESULTS: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus.
CONCLUSIONS: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.
Предметные рубрики MeSH
AnimalsAnticonvulsantsCA1 Region, HippocampalCerebral CortexDisease Models, AnimalDose-Response Relationship, DrugDrug Evaluation, PreclinicalFlavonoidsGlucosidesHemiplegiaHypnotics and SedativesMaleMiceMotor ActivityNeuroprotective AgentsRats, WistarRecovery of FunctionSeizuresTissue Culture Techniquesgamma-Aminobutyric Acid