title: The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes.
abstract: The usage of dietary supplements and other natural products to treat neurological diseases has been growing over time, and accumulating evidence suggests that flavonoids possess anticonvulsant properties. The aim of this study was to examine the effects of a flavonoid-rich extract from orange juice (OJe) in some rodent models of epilepsy and to explore its possible mechanism of action. The genetically audiogenic seizures (AGS)-susceptible DBA/2 mouse, the pentylenetetrazole (PTZ)-induced seizures in ICR-CD1 mice and the WAG/Rij rat as a genetic model of absence epilepsy with comorbidity of depression were used. Our results demonstrate that OJe was able to exert anticonvulsant effects on AGS-sensible DBA/2 mice and to inhibit PTZ-induced tonic seizures, increasing their latency. Conversely, it did not have anti-absence effects on WAG/Rij rats. Our experimental findings suggest that the anti-convulsant effects of OJe are likely mediated by both an inhibition of NMDA receptors at the glycine-binding site and an agonistic activity on benzodiazepine-binding site at GABAAreceptors. This study provides evidences for the antiepileptic activity of OJe, and its results could be used as scientific basis for further researches aimed to develop novel complementary therapy for the treatment of epilepsy in a context of a multitarget pharmacological strategy.
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. citraro@unicz.it.
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina I-98168, Italy. mnavarra@unime.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. aleo@unicz.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Leo
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. donatodipaola@unicz.it.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Donato Di Paola
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. santangelo@unicz.it.
authors.forename: Ermenegildo
authors.initials: E
authors.lastname: Santangelo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples I-80131, Italy. plippiello@gmail.com.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Lippiello
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. aiellorossana@gmail.com.
authors.forename: Rossana
authors.initials: R
authors.lastname: Aiello
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. erusso@unicz.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.affiliation: Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy. desarro@unicz.it.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
keywords: Citrus sinensis; absence epilepsy; audiogenic seizures; complementary and alternative medicines; flavonoids; natural products; orange; orange juice; spike-wave discharges