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Molecules 2016, 21(9), 1261; doi:10.3390/molecules21091261

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

1
Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro I-88100, Italy
2
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina I-98168, Italy
3
Department of Pharmacy, University of Naples Federico II, Naples I-80131, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 30 July 2016 / Revised: 31 August 2016 / Accepted: 9 September 2016 / Published: 21 September 2016
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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 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. View Full-Text
Keywords: orange; Citrus sinensis; flavonoids; audiogenic seizures; absence epilepsy; spike-wave discharges; natural products; complementary and alternative medicines; orange juice orange; Citrus sinensis; flavonoids; audiogenic seizures; absence epilepsy; spike-wave discharges; natural products; complementary and alternative medicines; orange juice
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Citraro, R.; Navarra, M.; Leo, A.; Donato Di Paola, E.; Santangelo, E.; Lippiello, P.; Aiello, R.; Russo, E.; De Sarro, G. The Anticonvulsant Activity of a Flavonoid-Rich Extract from Orange Juice Involves both NMDA and GABA-Benzodiazepine Receptor Complexes. Molecules 2016, 21, 1261.

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