Anti-inflammatory coumarins with short- and long-chain hydrophobic groups from roots of Angelica dahurica cv. Hangbaizhi

摘要

The H-1 NMR-guided fractionation of a cyclohexane soluble portion of the 75% ethanolic extract of the roots of Angelica dahurica cv. Hangbaizhi led to the isolation of two coumarins, namely, 5-(3"-hydroxy3"-methylbutyl)-8-hydroxyfuranocoumarin, and isobyakangelicin hydrate-3"-ethyl ether, and ten coumarins with short- or long-chain hydrophobic groups, namely, andafocoumarins A-J. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of the C-2" secondary alcohols in ten of these compounds were deduced via the circular dichroism data of the in situ formed [Rh-2(OCOCF3)(4)] complex, and oxidation reactions were utilized to determine location of the double bonds in the lipid chain of andafocoumarins H and 1, respectively. The long-chain hydrophobic group of andafocoumarin J was determined by the method of chemical degradation and GC-MS analysis. It was the first time that coumarins with short- or long-chain hydrophobic groups in this plant had been comprehensively investigated. All isolates were assayed for their inhibitory effect against nitric oxide (NO) production in a lipopolysaccharide (LPS)-activated RAW264.7 macrophage cell line, among which andafocoumarins A and B exhibited a potent inhibition on LPS-activated NO production with IC50 values of 19.7 and 13.9 mu M, respectively, indicating their stronger inhibitory activity than L-N-6-(1-iminoethyl)-lysine (IC50 = 23.7 mu M), a selective inhibitor of inducible nitric oxide synthase. (C) 2016 Elsevier Ltd. All rights reserved.