ABSTRACT
The methanolic extract (200 mg/kg, p.o. and i.p.), principal coumarin constituents (isoepoxypteryxin, anomalin, and praeroside IV), and a polyacetylene constituent (falcarindiol) (25 mg/kg, i.p.) from the roots of Angelica furcijuga protected the liver injury induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS) in mice. In in vitro experiments, coumarin constituents (hyuganins A-D, anomalin, pteryxin, isopteryxin, and suksdorfin) and polyacetylene constituents [(-)-falcarinol and falcarindiol] substantially inhibited LPS-induced NO and/or TNF-alpha production in mouse peritoneal macrophages, and isoepoxypteryxin inhibited D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. Furthermore, hyuganin A, anomalin, and isopteryxin inhibited the decrease in cell viability by TNF-alpha in L929 cells.
Subject(s)
Acetylene/pharmacology , Angelica/chemistry , Coumarins/pharmacology , Galactosamine/toxicity , Lipopolysaccharides/toxicity , Liver/drug effects , Macrophages, Peritoneal/drug effects , Nitric Oxide/biosynthesis , Plant Roots/chemistry , Animals , Cells, Cultured , Macrophage Activation , Macrophages, Peritoneal/metabolism , Male , Mice , Rats , Rats, Wistar , Tumor Necrosis Factors/biosynthesisABSTRACT
The methanolic extract from the flowers of Angelica furcijuga KITAGAWA was found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. From the methanolic extract, two new glycosides, hyuganosides IV and V, were isolated together with 28 known constituents. The structures of the new constituents were determined on the basis of chemical and physicochemical evidence. Furthermore, the inhibitory effects of 11 coumarin constituents on nitric oxide production were examined. Among them, 3'-angeloyl-cis-khellactone (IC(50)=82 microM), (S)-(-)-oxypeucedanin (57 microM), imperatorin (60 microM), isoepoxypteryxin (53 microM), and isopteryxin (8.8 microM) showed inhibitory activity.
Subject(s)
Angelica/chemistry , Benzofurans/chemistry , Benzofurans/pharmacology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Animals , Carbohydrate Conformation , Chromatography, High Pressure Liquid , Flowers/chemistry , Hydrolysis , In Vitro Techniques , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Plant Extracts/chemistry , Spectrophotometry, InfraredABSTRACT
Three new aromatics glycosides, hyuganosides II, IIIa, and IIIb, were isolated from a Japanese folk medicine, the roots of Angelica furcijuga KITAGAWA. The structures of the new glycosides were determined on the basis of chemical and physicochemical evidence.
