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 condi-tions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the in-duction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bi-oactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural cir-cuits 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 sup-ported 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.
Highlights
Epilepsy is a chronic brain disorder having multifaceted underlying causes
The aim of the current antiepileptic drugs (AEDs) therapy is to abolish seizures, without altering the normal functions. It is evident from the previous studies that several members of flavonoid family are capable of modulating the cAMP response element binding protein (CREB)-Brain derived neurotrophic factor (BDNF) pathway and influence various neurological processes
CREB is found within almost all neural circuits and influences the expression of a wide spectrum of genes, general alterations in CREB function cannot be expected to produce uniform effects throughout the central nervous system
Summary
Epilepsy is a chronic brain disorder having multifaceted underlying causes. Abnormal electric discharge usually occurs as a result of different perinatal and postnatal injuries of neuronal circuits. A number of new medicines have been identified that can be used along with the conventional AED therapy for the management of drug resistant epilepsy like, oxcarbazepine, levetiracetam, lacosamide, stiripentol, retigabine, eslicarbazepine, brivaracetam and ganaxolone, etc. Their efficacy cannot be considered superior to the first-generation AEDs [7]. Flavonoids exert a strong antiinflammatory action by exhibiting free-radical scavenging activity in the brain or by directly altering the neuroinflammatory cascades [15] Apart from their antioxidant and antiinflammatory potential, flavonoids act on a number of targets involved in the pathogenesis of epilepsy including, GABA receptors, opioid receptors, N-methyl-D-aspartate (NMDA) receptors, calcium and sodium ion channels [16]
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