Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy

Abstract

cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway.