GABAergic phthalide dimers from Angelica sinensis (Oliv.) Diels.
The methanol extract of Angelica sinensis (Oliv.) Diels roots (Dang Gui) has been shown to exhibit competitive binding to the GABAa receptor, suggesting the presence of GABAergic ligands. Chromatographic fractionation of the methanol extract led to the isolation of two GABAergic dimeric phthalides 1 and 2. Gelispirolide (1) was elucidated as a new phthalide dimer composed of a Z-ligustilide and a Z-butylidenephthalide unit on the basis of spectroscopic approaches including one- and two-dimensional NMR, HRESIMS and HRESIMS-MS. Compound 2 was identified as the known dimeric phthalide, riligustilide, by comparison of its spectroscopic data with literature values. Its dimeric linkage and stereochemistry were ascertained by a single crystal X-ray diffraction experiment. Both dimers 1 and 2 were found to be active in an in vitro GABAa receptor-binding assay with IC50 values of 29 and 24 microM, respectively.
Deng
Shixin
S
UIC/NIH Center for Botanical Dietary Supplements Research and Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, M/C 781, Chicago, IL 60612, USA.
Chen
Shao-Nong
SN
Lu
Jian
J
Wang
Zaijie Jim
ZJ
Nikolic
Dejan
D
van Breemen
Richard B
RB
Santarsiero
Bernard D
BD
Mesecar
Andrew
A
Fong
Harry H S
HH
Farnsworth
Norman R
NR
Pauli
Guido F
GF
D029971:Angelica sinensis / Q000737:chemistry*; D001572:Benzofurans / Q000737:chemistry*; D018682:GABA Agents / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism
D001572:Benzofurans; D018682:GABA Agents; D011963:Receptors, GABA-A; C517986:gelispirolide; C517987:riligustilide