In vitro GABA-transaminase inhibitory compounds from the root of Angelica dahurica

The 80% aqueous MeOH extracts from the root of Angelica dahurica, found to inhibit the activities of GABA degradative enzymes GABA transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH), were fractionated using EtOAc, n-BuOH and H₂O. Repeated column chromatography for the EtOAc and n-BuOH fractions led to the isolation of two new coumarins, oxypeucedanin hydrate-3″-butyl ether and isopraeroside IV along with six known coumarins, isoimperatorin, imperatorin, phellopterin, oxypeucedanin hydrate, nodakenin and 3′-hydroxymarmesinin, and two polyacetylenes, falcarindiol and octadeca-1,9-dien-4,6-diyn-3,8,18-triol. Of the isolated pure compounds, imperatorin and falcarindiol inactivated the GABA-T activities in both time- and concentration-dependent manners. The kinetic studies showed that imperatorin and falcarindiol reacted with the GABA-T with a second-order rate constant of 2.3 ± 0.2 mM^-1 min^-1 and 1.5 ± 0.1 mM ^-1 min^-1, respectively. It is postulated that imperatorin and falcarindiol are able to elevate the neurotransmitter GABA levels in the central nervous system by an inhibitory action on the GABA degradative enzyme GABA-T.