title: Inhibition of airway inflammation by the roots of Angelica decursiva and its constituent, columbianadin.
abstract: BACKGROUND
  The roots of Angelica decursiva Fr. Et Sav (Umbelliferae) have been frequently used in traditional medicine as anti-inflammatory, antitussive, analgesic agents and expectorant, especially for treating cough, asthma, bronchitis and upper respiratory tract infections. To establish the scientific rationale for the clinical use of Angelica decursiva and to identify new agents for treating inflammatory lung disorders, pharmacological evaluation of the roots of Angelica decursiva and the isolated constituents was performed.
  
  
  METHODS
  In vitro study was carried out using two lung cells, lung epithelial cells (A549) and alveolar macrophages (MH-S). The inflammatory markers such as IL-6 and nitric oxide (NO) for each cell line were examined. For in vivo study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used and the effects on lung inflammation were established by measuring the cell numbers in bronchoalveolar lavage fluid (BALF) and by histological observation.
  
  
  RESULTS
  Water and 70% ethanol extracts of the roots of Angelica decursiva showed considerable inhibitory activity against LPS-induced lung inflammation in mice following oral administration at a dose of 400 mg/kg. Five coumarin derivatives including columbianadin, umbelliferone, umbelliferone 6-carboxylic acid, nodakenin and nodakenetin were isolated. Among the isolated compounds, columbianadin was found to possess strong inhibitory activity against the inflammatory response of IL-1β-treated A549 cells and LPS-treated MH-S cells. Columbianadin was found to inhibit NO production by down-regulation of inducible NO synthase. Moreover, columbianadin was also proved to possess significant inhibitory activity against LPS-induced lung inflammation following oral administration at a dose of 20-60 mg/kg.
  
  
  CONCLUSIONS
  The roots of Angelica decursiva were proved to be effective in the treatment of lung inflammation. Columbianadin can be a potential new agent for treating inflammatory lung disorders.
authors: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Hun Jai
authors: HJ
authors: Lim
authors: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Ju Hee
authors: JH
authors: Lee
authors: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors: Jae Sue
authors: JS
authors: Choi
authors: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Sang Kook
authors: SK
authors: Lee
authors: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Yeong Shik
authors: YS
authors: Kim
authors: College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea. Electronic address: hpkim@kangwon.ac.kr.
authors: Hyun Pyo
authors: HP
authors: Kim
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D029969:Angelica / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D004731:Endotoxins; D018836:Inflammation Mediators; D015850:Interleukin-6; D010936:Plant Extracts; D012997:Solvents; C577686:interleukin-6, mouse; D014867:Water; D009569:Nitric Oxide; D000431:Ethanol; C064386:columbianadin; C044101:endotoxin, Escherichia coli; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Angelica decursiva; Columbianadin; Coumarin; Lung inflammation