Strategy for the isolation and identification of coumarins with calcium antagonistic properties from the roots of Angelica archangelica

Abstract

Fifteen coumarins, 2′‐angeloyl‐3′‐isovaleryl vaginate (4), archangelicin (3), oxypeucedanin hydrate (8), bergapten (5), byakangelicin angelate (15), imperatorin (11), isoimperatorin (6), isopimpinellin (13), 8‐[2‐(3‐methylbutroxy)‐3‐hydroxy‐3‐methylbutoxy]psoralen (12), osthol (1), ostruthol (9), oxypeucedanin (7), phellopterin (14), psoralen (2) and xanthotoxin (10), have been isolated from a chloroform extract of the roots of Angelica archangelica L. subsp. archangelica (Apiaceae). 2, 4, 12, and 15 are reported for the first time from A. archangelica L. The isolation was carried out using medium pressure liquid chromatography (MPLC) using the normal phase mode and then subsequently using a combination of the reversed and normal phase techniques. The eluents were optimized by thin layer chromatography and high performance liquid chromatography preassays according to the “PRISMA” system, and then transferred without modification of the solvent selectivity to preparative MPLC separations. The structures of the compounds were elucidated by a combination of spectroscopic methods. The isolation was carried out from a chloroform extract which in earlier tests had exhibited calcium blocking activity on the uptake of 45Ca2+ in clonal rat pituitary GH4C1 cells. The calcium antagonistic activity of the isolated compounds was then tested using the same method as for the extracts. All the coumarins tested exhibited calcium antagonistic activity. Archangelicin showed activity significantly higher than that of verapamil in this test system.

Miniaturisation and validation of a cell-based assay for screening of Ca2+ channel modulators

“…500-fold more effective in inhibiting the 45 Ca 2 + entry in GH 4 C 1 cells (Table 2, IC 50 values 0.007 and 3.4 AM, respectively). The IC 50 value obtained for verapamil is in accordance with our previous results and literature data on this inhibitor (4.2 AM [13], 4.1 AM [10], and 1 AM [26]). The dose -response curves for these compounds are presented in Fig.…”

Epilepsy in the Renaissance: A survey of remedies from 16th and 17th century German herbals

“…Subsequently, fifteen furocoumarins were isolated and tested. The most potent calcium uptake antagonist was archangelicin (Härmälä et al, 1992). The anticonvulsive activity of imperatorin from the fruits of A. archangelica was tested in mice, where the threshold of MES induced seizures was measured after 15, 30, 60 and 120 min.…”

Furanocoumarins

“…Glowniak et al [37] demonstrated that the application of mixed binary or ternary solvents of dichloromethane, chloroform, trichloroethylene, ether, petrol, and tetrachloromethane leads to a significant increase in the extraction efficiency. Härmälä et al [38] investigated 20 organic solvents to apply them in the extraction of coumarins from the root of A. archangelica. Physicochemical parameters, such as density, viscosity, surface tension, and number of carbon atoms in a molecule, were compared in relation to concentrations of polar and no polar substances obtained in extraction processes.…”

“…The fluid is characterized by a high diffusion coefficient, low viscosity and density, and lack of surface tension. The fluid has very good penetration and the ability to dissolve the substances in this matrix [38,41].…”