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

The dietary flavonoids apigenin, genistein and (-)-epigallocatechin gallate (EGCG) inhibited the activation by GABA (40 muM) of recombinant human alpha1beta2gamma2L GABA(A) receptors expressed in Xenopus laevis oocytes with IC50 values of 8, 30 and 15 muM, respectively. Apigenin and genistein also acted as GABA antagonists at flumazenil-insensitive alpha1beta2 GABA(A) receptors, indicating that they were not acting as negative modulators through flumazenil-sensitive benzodiazepine sites on GABA(A) receptors. In addition to these GABA(A) antagonist effects, a novel second order modulatory action was found for apigenin and EGCG on the first order enhancement of GABA responses by diazepam. Apigenin (1 muM) and EGCG (0.1 muM) enhanced the modulatory action of diazepam (3 muM) on the activation by GABA (5 muM) of recombinant human alpha1beta2gammaL GABA(A) receptors by up to 22% and 52%, respectively. This was not found with genistein, nor was it observed with enhancement by allopregnanolone or pentobarbitone. (C) 2004 Elsevier Inc. All rights reserved.