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

Rita Citraro,Rossana Aiello,Eugenio Donato Di Paola,Ermenegildo Santangelo,Emilio Russo,Antonio Leo,Michele Navarra,Pellegrino Lippiello,Giovambattista De Sarro

doi:10.3390/molecules21091261

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.

Highlights

Epilepsy is one of the most common serious neurological disorders encountered in clinical practice
Very recently we studied the antioxidant activity of a flavonoid-rich extract from half-blood orange juice (OJe), demonstrating its capability to: (i) reduce the levels of both reactive oxygen species and membrane lipid peroxidation; (ii) improve mitochondrial functionality and (iii) prevent DNA-oxidative damage in A549 cells incubated with H2 O2 [13]
Study,for forthe the first time, we report the anticonvulsant effects of aa flavonoid-rich flavonoid-rich extract

Summary

Introduction

Epilepsy is one of the most common serious neurological disorders encountered in clinical practice. It is known that both GABA and glutamate receptors may play an important role in seizure initiation, maintenance and arrest [1]. Excessive activation of excitatory amino-acid receptors determines the generation of reactive oxygen (ROS) and reactive nitrogen (RNS) species that in turn can provoke seizure genesis and related cell death [2,3]. Intervention with antioxidants could be a potential beneficial approach in the treatment of epilepsy [4]. Previous studies have suggested a protective role of antioxidants, such as ascorbic acid, vitamin E, α-tocopherol, curcumin, trans-resveratrol, melatonin and α-lipoic acid against seizures induced by different convulsive agents [5,6,7].

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