Coumarins from Angelica decursiva Inhibit Lipopolysaccharide‐induced Nitric Oxide Production in RAW 264.7 Cells

Abstract

Angelica decursiva has been used in Korean traditional medicine as an antitussive, analgesic, antipyretic, and cough remedy. In a recent study, the 90% methanol fraction of the dichloromethane fraction showed the most promising anti‐inflammatory activity; however, compounds responsible for the anti‐inflammatory activity were not identified. In this study, bioactivity‐guided isolation yielded 8 coumarins along with a new coumarin, 3′‐angeloyloxy‐4′‐hydroxy‐3′,4′‐dihydroxanthyletin (4). The anti‐inflammatory activity of compounds was evaluated via inhibition of nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) expression in lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells. Among the tested compounds, edulisin II (1) exhibited the highest NO inhibitory activity, followed by decursidin (2), Pd‐C‐III (3), 4, Pd‐C‐I (5), and Pd‐C‐II (6). Structure‐activity relationships revealed that esterification of the hydroxyl at C‐3′/C‐4′ with an angeloyl/senecioyl/acetyl is essential for NO inhibitory activity; the number and the position of angeloyl/or senecioyl groups greatly affect the potency of coumarins. Coumarins 1~6 inhibited TNF‐α production and iNOS expression while 1~4 inhibited COX‐2 expression. Thus, coumarins isolated from A. decursiva might be used as potential leads for the development of therapeutic agents for inflammation.