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.

Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

“…Several external stimuli that activate the intracellular pathways (like activation of PI3K/Akt, Ca 2+/CAM or PLC/IP3 signaling pathway, NMDA activation) result in the phosphorylation of CREB which provokes transcription of bdnf . Bdnf acts through its TrkB receptor to initiate a downstream row of events ( Sharma et al, 2019 ). Previous reports have recognized that bdnf is strongly expressed in the brain of 7 dpf zebrafish larvae ( Cacialli et al, 2016 ).…”

“…The receptors for GABA and glutamate (NMDA receptors) are very crucial targets for antiepileptic drug research. Activation of NMDA receptors leads to calcium-calmodulin dependent CREB phosphorylation ( Sharma et al, 2019 ). GABA neurotransmission is also associated with BDNF/TrkB activation.…”

The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial

“…Previous animal studies [ 36 , 46 ] highlighted that quercetin and Q3G significantly increased the mRNA expression and secretion of BDNF in rats, which contribute to the neural stem cell proliferation. The possible underlying mechanism could be the quercetin activates BDNF-TrkB and its associated signaling pathway, which eventually, results in phosphorylation of CREB, followed by an increase in extracellular signal-regulated kinase (ERK) and BDNF [ 47 , 48 ]. Therefore, quercetin interactions with these pathways may be responsible for its role in the central nervous system.…”

Antidementia Effects of Alternanthera philoxeroides in Ovariectomized Mice Supported by NMR-Based Metabolomic Analysis

“…The whole plant is also consumed as a vegetable for health tonic in Southeast Asia [ 12 , 13 ]. Moreover, the ethanol extract of A. philoxeroides is claimed for its capacity to improve menopausal depression due to its flavone constituents that exert effects on neurogenesis and neuroplasticity process via estrogen receptor-mediated reinforcement of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) gene transcription in the hippocampus and frontal cortex [ 14 ]. Additionally, these flavonoids also displayed an inhibitory effect on monoamine oxidases (MAO)-A and -B that influence the level of serological neurotransmitters [ 15 ].…”