In vitro GABA-transaminase inhibitory compounds from the root ofAngelica dahurica

Abstract

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.

Effect of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of classical antiepileptic drugs against maximal electroshock-induced seizures in mice

“…It has been suggested that imperatorin may complementary potentiate the anticonvulsant activity of carbamazepine, phenytoin and phenobarbital in experimental animals through imperatorin-induced irreversible inactivation of GABA-transaminase and subsequent increase in GABA content in the brain [14,36]. Moreover, imperatorin enhances GABA-mediated inhibitory neurotransmitter action through the interaction with benzodiazepine receptors [37].…”

Simultaneous determination and pharmacokinetics of sixteen Angelicae dahurica coumarins in vivo by LC–ESI-MS/MS following oral delivery in rats

“…As a class of natural products, coumarins have attracted considerable interest for their various pharmacological activity in recent years. Imperatorin has anti-cancer activity as well as anticonvulsant potential due to increasing level of gamma-aminobutyric acid (GABA) in vitro (Choi et al 2005;Łuszczki et al 2010;Kleiner et al 2001;Yang et al 2006). Isoimperatorin demonstrates various pharmacological effects of anti-inflammatory, analgesic, antispasmodic and anticancer activities (Chen et al 1995;Moon et al 2011;Moon et al 2008;Wang et al 2010).…”

In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine

“…Isopraeroside IV is a coumarin isolated from the root of Angelica dahurica [45]. 9HFG originates from the root of Dictamnus dasycarpus , which has been used as a folk remedy for inflammation and skin ailments [46].…”