title: Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva.
abstract: OBJECTIVE
  We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo.
  
  
  METHODS
  The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model.
  
  
  RESULTS
  UMC dose-dependently inhibited NO and PGE(2) production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC(50) value of 705.1 μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.
  
  
  CONCLUSIONS
  The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.forename: Ran Joo
authors.initials: RJ
authors.lastname: Choi
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Jin
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Ahn
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhao
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D029969:Angelica; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007249:Inflammation / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008517:Phytotherapy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014468:Umbelliferones; C578831:umbelliferone 6-carboxylic acid; D009569:Nitric Oxide; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone