The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes

• Main Authors: Rita Citraro, Michele Navarra, Antonio Leo, Eugenio Donato Di Paola, Ermenegildo Santangelo, Pellegrino Lippiello, Rossana Aiello, Emilio Russo, Giovambattista De Sarro
• Format: Article
• Language: English
• Published: MDPI AG 2016-09-01
• Series: Molecules
• Subjects: orange; Citrus sinensis; flavonoids; audiogenic seizures; absence epilepsy; spike-wave discharges; natural products; complementary and alternative medicines; orange juice
• Online Access: http://www.mdpi.com/1420-3049/21/9/1261

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 GABAA receptors. 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.