Investigation of the chemical constituents of some medicinal plants acting on different GABAA receptor subtypes

Abstract

Natural products have immense potential in drug discovery so the present study investigated the activity of extracts and phytochemicals from three medicinal plants, and some semi-synthetic analogues, on recombinant GABAA receptors expressed in Xenopus laevis oocytes. Asiatic 40 and madecassic acids 41 from Centella asiatica, had substantial differences in their modulation of GABA-induced current. Asiatic acid negatively modulated the GABA-induced current with IC50s of 37, 64, and 427µM at α1β2γ2L, α5β3γ2L, α2β2γ2L receptors, respectively. On the contrary, madecassic acid only inhibited the GABA-induced current at α2β2γ2L (IC50, 428µM) receptor. Among the semi-synthetic analogues, the asiatic acid amide 158 negatively modulated the GABA-induced current with enhanced negative modulation at α1β2γ2L (IC50, 14µM) and α2β2γ2L (IC50, 28µM) receptors. All compounds from Passiflora incarnata negatively modulated the GABA-induced current, except kaempferol 72, with the greatest inhibition by isoorientin 85, which inhibited the EC10 GABA-induced current at α2β2γ2L receptor by 48.2 ± 0.77%. Resveratrol from Vitis vinifera (at 100μM) induced small current (22.0 ± 3.5 nA) and potentiated the GABA-induced current at α1β2γ2L receptor, with an EC50 of 58μM, while trans-ε-viniferin negatively modulated the GABA-induced at all three subtypes, with IC50s of 5.8, 19, 21μM on α1β2γ2L, α2β2γ2L, and α5β3γ2L receptors, respectively.