The dietary flavonoids apigenin and (−)-epigallocatechin gallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABAA receptors

Flavonoid Actions on Receptors for the Inhibitory Neurotransmitter GABA

“…The inhibition of the GABA response at α1β2γ2S GABA A receptors expressed in oocytes in the presence of lumazenil (0.1-1 mM) was the irst deinitive report of the lumazenil-insensitive actions of lavonoids on recombinant GABA A receptors [10]. Similar lumazenil-insensitive negative modulatory actions of apigenin on recombinant GABA A receptors were subsequently reported by other investigators [11,23].…”

“…Functional electrophysiological studies have also demonstrated that apigenin can act as a second-order modulator of the irst-order modulation of GABA A receptors by benzodiazepines [11]. This efect of apigenin was observed at concentrations where apigenin alone had no detectable modulatory efects on GABA responses.…”

“…The genes coding for the three GABA C subunits are found on diferent chromosomes to those coding for GABA A subunits. Modulators of GABA C receptors are rare (zinc, lanthanides and some neurosteroids), although some lavonoids have been show to inhibit GABA C receptors, for example, apigenin and quercetin [10,11]. GABA A and GABA C receptors have distinct pharmacological proiles, with some agents having opposite efects (agonist/antagonist) on the two classes of receptors.…”

“…naringenin [22]) and lavanols (e.g. epigallocatechin gallate (EGCG) [11]). Each of the lavonoids listed is known to inluence GABA A receptors and to produce CNS efects.…”

Hill coefficients of dietary polyphenolic enzyme inhibitiors: can beneficial health effects of dietary polyphenols be explained by allosteric enzyme denaturing?

“…From our literature searches compiling Hill coefficients of polyphenol enzyme interactions, the following observations were made: [24], glutamate dehydrogenase [25], ATP-sensitive potassium channels [26], rat brain Kv 1.5 potassium channels [27], DNA methyltransferase 1a [28], apigenin binding to GABA receptors [29], phloridzin inhibiting SGLT-1 [30], Genistein-inhibiting calf uterus estrogen receptor [31] and various tyrosine kinases [32][33][34], Luteolin binding to the Benzodiazepin receptor [35], and finally, 5-caffeoyl quinic acid inhibiting a series of non-human enzymes such as Helianthinin [36], sunflower 11S protein [37], diphenol oxidase [38], and phenylalanine ammonia lyase from potato [39]. 4.…”