title: Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitrite oxide production in RAW 264.7 cells.
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.
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors.forename: Ishrat Jahan
authors.initials: IJ
authors.lastname: Ishita
authors.affiliation: Department of Pharmacy, Mawlana Bhashani Science and Technology University, Santosh, Tangail, 1902, Bangladesh.
authors.forename: Md
authors.initials: M
authors.lastname: Nurul Islam
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, 151-742, Republic of Korea.
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Angiogenesis & Chinese Medicine Laboratory, Department of Pharmacology, University of Cambridge, Cambridge, UK.
authors.forename: Ran Joo
authors.initials: RJ
authors.lastname: Choi
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Hee Sook
authors.initials: HS
authors.lastname: Sohn
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea. jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.affiliation: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea. choijs@pknu.ac.kr.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D029969:Angelica; D000818:Animals; D003374:Coumarins / Q000302:isolation & purification* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D010936:Plant Extracts / Q000302:isolation & purification* / Q000494:pharmacology; D000067996:RAW 264.7 Cells
chemical_list: D003374:Coumarins; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide
keywords: Angelica decursiva; Anti-inflammation; Coumarin; Nitric oxide; RAW 264.7 cell