Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells.
Journal: 2016/October - Archives of Pharmacal Research
ISSN: 0253-6269
Abstract:
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.
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