Epilepsy is a
brain disorder that affects millions of people worldwide and is usually managed using currently available
antiepileptic drugs, which result in adverse effects and are ineffective in approximately 20-25% of patients. Thus, there is growing interest in the development of new
antiepileptic drugs with fewer side effects. In a previous study, we showed that a Rehmannia glutinosa (RG) water extract has protective effects against electroshock- and
pentylenetetrazol (PTZ)-induced
seizures, with fewer side effects. In this study, the objective was to identify the RG components that are responsible for its
anticonvulsant effects. Initially, a number of RG components (
aucubin,
acteoside,
catalpol, and
mannitol) were screened, and the
anticonvulsant effects of different doses of
catalpol,
mannitol, and their combination on electroshock- and chemically (PTZ or
strychnine)-induced
seizures in mice, were further assessed.
Gamma-aminobutyric acid (
GABA) receptor binding assay and electroencephalography (EEG) analysis were conducted to identify the potential underlying drug mechanism. Additionally, treated mice were tested using open-field and rotarod tests.
Catalpol,
mannitol, and their combination increased threshold against electroshock-induced
seizures, and decreased the percentage of seizure responses induced by PTZ, a
GABA antagonist.
GABA receptor binding assay results revealed that
catalpol and
mannitol are associated with
GABA receptor activity, and EEG analysis provided evidence that
catalpol and
mannitol have
anticonvulsant effects against PTZ-induced
seizures. In summary, our results indicate that
catalpol and
mannitol have
anticonvulsant properties, and may mediate the protective effects of RG against
seizures.