Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells.
Märksõnad
Abstraktne
Angelica decursiva has long been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy. In this study, the anti-inflammatory activity of 9 coumarin derivatives isolated from a 90 % methanol fraction was evaluated via inhibition of production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Among the tested compounds, edulisin II (1) exhibited the most potent NO production inhibitory activity, followed by decursidin (2), Pd-C-III (3), 4-hydroxy Pd-C-III (4), Pd-C-I (5), and Pd-C-II (6). In contrast, (+)-trans-decursidinol (7) did not exhibit NO suppressive effects on LPS-stimulated RAW 264.7 cells. Structure-activity relationships revealed that esterification of the hydroxyl at C-3' or C-4' of 7 with an angeloyl/senecioyl/acetyl group is essential for its inhibitory activity against NO production, while the number of angeloyl or senecioyl groups, and their positions greatly affect the potency of these coumarins. Coumarins 1-6 also inhibited TNF-α production and iNOS protein expression, while compounds 1-4 inhibited COX-2 protein expression in LPS-stimulated RAW 264.7 cells. These results suggest that coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation-associated disorders.