Flavonoid modulation of GABA_A receptors

Abstract

There has been a resurgence of interest in synthetic and plant-derived flavonoids as modulators of g-amino butyric acid-A (GABAA) receptor function influencing inhibition mediated by the major inhibitory neurotransmitter GABA in the brain. Areas of interest include (i) flavonoids that show subtype selectivity in recombinant receptor studies in vitro consistent with their behavioural effects in vivo, (ii) flumazenil-insensitive modulation of GABAA receptor function by flavonoids, (iii) the ability of some flavonoids to act as second-order modulators of first-order modulation by benzodiazepines and (iv) the identification of the different sites of action of flavonoids on GABAA receptor complexes. An emerging area of interest is the activation of GABAA receptors by flavonoids in the absence of GABA. The relatively rigid shape of flavonoids means that they are useful scaffolds for the design of new therapeutic agents. Like steroids, flavonoids have wide-ranging effects on numerous biological targets. The challenge is to understand the structural determinants of flavonoid effects on particular targets and to develop agents specific for these targets.

Neuropharmacological studies on ethyl acetate fraction of Securinega virosa root bark extract

“…Previous works have reported the anticonvulsant and sedative properties of flavonoids (Johnston, 2005;Yao et al, 2010;Hanrahan et al, 2011). Flavonoids, found to be present in the ethyl acetate fraction of methanol root bark extract of S. virosa, may therefore be responsible for the observed anticonvulsant and sleep promoting activities.…”

Anticonvulsant and anxiolyic activities of ethyl acetate fraction of Cassia fistula Linn. pods in mice

“…30 The present work showed the dose dependent anxiolytic effect as evidenced from the significant increase in the frequency and time spent in open arms by the animals treated with 50 and 100 mg/kg of EAFCF orally. Since, benzodiazepines are used for validating this animal model 30 and flavonoids are believed to modulate GABAergic system, 31 it is suggested that EAFCF, being rich in flavonoids, may produce its anxiolytic activity by acting on GABA A receptor mediated GABAergic system. To investigate the role of GABAergic system, flumazenil (GABA A receptor antagonist) was administered before the treatment of EAFCF and the results showed that the pretreatment of flumazenil blocked the anxiolytic effect of EAFCF in EPM.…”

“…Loeselia Mexicana, 32 Piper methysticum, 33 Euphorbia hirta, 34 and Cymbopogon citratus) have also been reported to mediate their anxiolytic activity through GABAergic system. 31,35 The open-field test is based on the rodents intrinsic behaviour to stay near the periphery of a novel environment (ie. thigmotaxis), which may provide the animal a sense of security.…”

Flavonoid Actions on Receptors for the Inhibitory Neurotransmitter GABA

“…Thus, lavonoids can inluence GABA A receptors via the classical benzodiazepine-binding site, as well as independently of the classical benzodiazepine-binding site [3,16]. Many lavonoids elicit biphasic responses, enhancing GABA actions at low concentrations and inhibiting at high concentrations.…”