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

• Published in: Phytotherapy research 2005-10, Vol.19 (10), p.839-845
• Main Authors: Choi, Soo Young, Ahn, Eun-Mi, Song, Myoung-Chong, Kim, Dae Won, Kang, Jeong Han, Kwon, Oh-Shin, Kang, Tae-Cheon, Baek, Nam-In
• Format: Article
• Language: English
• Subjects: 4-Aminobutyrate Transaminase - antagonists & inhibitors; Angelica; Angelica dahurica; Animals; Biological and medical sciences; Brain - enzymology; Cattle; Coumarins - administration & dosage; Coumarins - chemistry; Coumarins - pharmacology; Coumarins - therapeutic use; GABA transaminase (GABA-T); General pharmacology; Glucosides - administration & dosage; Glucosides - chemistry; Glucosides - pharmacology; Glucosides - therapeutic use; Infusions, Intravenous; isopraeroside IV; Medical sciences; oxypeucedanin hydrate-3″-butyl ether; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phytotherapy; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Roots; Succinate-Semialdehyde Dehydrogenase - antagonists & inhibitors; Umbelliferae
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.1424

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. Copyright © 2005 John Wiley & Sons, Ltd.