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|Title: ||Investigation of the chemical constituents of some medicinal plants acting on different GABAA receptor subtypes|
|Authors: ||Hamid, Kaiser|
|Issue Date: ||27-Mar-2015|
|Publisher: ||University of Sydney|
Faculty of Pharmacy
|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.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
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|HAMID Kaiser - Final Thesis.pdf||Thesis||46.06 MB||Adobe PDF|
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