Methylated flavonoids as anti-seizure agents: Naringenin 4 ′,7-dimethyl ether attenuates epileptic seizures in zebrafish and mouse models

Publication date: Available online 22 November 2017 Source:Neurochemistry International Author(s): Daniëlle Copmans, Adriana M. Orellana-Paucar, Gert Steurs, Yifan Zhang, Annelii Ny, Kenn Foubert, Vasiliki Exarchou, Aleksandra Siekierska, Youngju Kim, Wim De Borggraeve, Wim Dehaen, Luc Pieters, Peter A.M. de Witte Epilepsy is a neurological disease that affects more than 70 million people worldwide and is characterized by the presence of spontaneous unprovoked recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail to control seizures in 30% of patients due to drug resistance. Hence, safer and more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures naturally present in most plants and consumed daily with no adverse effects reported. These structures have shown activity in several seizure and epilepsy animal models through allosteric modulation of GABAA receptors, but also via potent anti-inflammatory action in the brain. As such, dietary flavonoids offer an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability. It has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, thereby dramatically enhancing metabolic stability and membrane transport, facilitating absorption and highly increasing bioavailability. Since no scientific data is available ...
Source: Neurochemistry International - Category: Neuroscience Source Type: research