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.
Choi
Soo Young
SY
Department of Biomedical Sciences, Division of Life Sciences, Hallym University, Chuncheon 200-702, Korea.
Ahn
Eun-Mi
EM
Song
Myoung-Chong
MC
Kim
Dae Won
DW
Kang
Jeong Han
JH
Kwon
Oh-Shin
OS
Kang
Tae-Cheon
TC
Baek
Nam-In
NI
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D029969:Angelica; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D050644:Succinate-Semialdehyde Dehydrogenase / Q000037:antagonists & inhibitors
D003374:Coumarins; D005960:Glucosides; D010936:Plant Extracts; C574016:isopraeroside IV; D050644:Succinate-Semialdehyde Dehydrogenase; D000612:4-Aminobutyrate Transaminase