title: Antitussive, expectorant and anti-inflammatory activities of four alkaloids isolated from Bulbus of Fritillaria wabuensis.
abstract: BACKGROUND
  Bulbus Fritillaria Cirrhosae (BFC), known by the Chinese name "Chuan-Bei-Mu", is used as an antitussive, antiasthmatic and expectorant drug for more than 2000 years in China, and Bulbus of Fritillaria wabuensis S. Y. Tang & S. C. Yueh (BFW) was recorded in the 2010 edition of China Pharmacopoeia as one of sources for BFC. The primary objective of this study was to evaluate the antitussive, expectorant and anti-inflammatory effects of alkaloids - imperialine, imperialine-β-N-oxide, isoverticine, and isoverticine-β-N-oxide, which were isolated from BFW, and to provide experimental evidence for its traditional use.
  
  
  METHODS
  The alkaloids were isolated using phytochemical methods, and their structures were determined by spectroscopic analysis. Their antitussive effects were measured using murine model of ammonia induced cough, the expectorant effects were evaluated by measuring mice's tracheal phenol red output, and the anti-inflammatory effects were assessed by using the murine model of xylene induced ear edema.
  
  
  RESULTS
  The structures of the four alkaloids - imperialine, imperialine-β-N-oxide, isoverticine, and isoverticine-β-N-oxide isolated from BFW were confirmed. The four alkaloids significantly inhibited cough frequency and increased latent period of cough in mice induced by ammonia. Imperialine and isoverticine showed obviously antitussive activities in a dose-dependent manner. Besides, the four alkaloids markedly enhanced mice's tracheal phenol red output in expectorant assessment and significantly inhibited the development of ear edema in anti-inflammatory evaluation assay. Moreover, significant differences were found between the structure-activity relationships of the four alkaloids.
  
  
  CONCLUSIONS
  The four alkaloids exhibited significant antitussive, expectorant and anti-inflammatory activities. We suggest that they may be the active ingredients of BFW. The results of the present study provided evidence for BFW to be used as an antitussive and expectorant Traditional Chinese Medicine (TCM).
authors.affiliation: Department of Pharmacogonosy, West China College of Pharmacy, Sichuan University, No. 17, Duan 3, Renmin Nan Road, Chengdu 610041, PR China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Xu
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhu
authors.forename: Lihuan
authors.initials: L
authors.lastname: Nie
authors.forename: Xia
authors.initials: X
authors.lastname: Long
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000627:therapeutic use*; D000641:Ammonia; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D000996:Antitussive Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005100:Expectorants / Q000302:isolation & purification / Q000627:therapeutic use*; D005260:Female; D031410:Fritillaria / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D010637:Phenolsulfonphthalein / Q000378:metabolism; D008517:Phytotherapy; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D014992:Xylenes
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D000996:Antitussive Agents; D004365:Drugs, Chinese Herbal; D005100:Expectorants; D014992:Xylenes; D000641:Ammonia; D010637:Phenolsulfonphthalein