title: Antitussive, expectorant, and anti-inflammatory activities of four caffeoylquinic acids isolated from Tussilago farfara.
abstract: BACKGROUND
  The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and asthmatic conditions.
  
  
  OBJECTIVE
  The objective of this study is to isolate four caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate their antitussive, expectorant, and anti-inflammatory activities.
  
  
  METHODS
  The structures of compounds 1-4 isolated from EtE were determined by spectral analysis. Mice were orally treated with these compounds and their mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20 mg/kg once daily for 3 d. The antitussive and expectorant activities were evaluated separately with the ammonia liquor-induced model and the phenol red secretion model. The anti-inflammation activity was evaluated using leukocyte count in the bronchoalveolar lavage fluid after ammonia liquor-induced acute airway inflammation.
  
  
  RESULTS
  The four compounds were identified as chlorogenic acid (1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5-dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition in cough frequency), showed a significant antitussive effect. However, the mixture was the most effective to inhibit the cough frequency by 61.7%. All compounds also showed a significant expectorant effect, while compound 2 was the most potent to enhance the phenol red secretion by 35.7%. All compounds significantly alleviated inflammation, but compound 4 showed the strongest effect to inhibit the leukocytosis by 49.7%.
  
  
  CONCLUSIONS
  The caffeoylquinic acids and their mixture, exhibiting significant antitussive, expectorant, and anti-inflammatory effects, could be considered as the main effective ingredients of FTF, and they may act in a collective and synergistic way.
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Qi-Zhen
authors.initials: QZ
authors.lastname: Wu
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Zhao
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiang
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Mian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Chao-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: a Research Department of Pharmacognosy , China Pharmaceutical University , Nanjing , China.
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Xu
mesh_terms: D000085:Acetates / Q000737:chemistry; D000641:Ammonia; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology; D000996:Antitussive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005100:Expectorants / Q000302:isolation & purification / Q000494:pharmacology*; D035264:Flowers; D007964:Leukocytosis / Q000139:chemically induced / Q000517:prevention & control; D008813:Mice, Inbred ICR; D010637:Phenolsulfonphthalein; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D031207:Tussilago / Q000737:chemistry
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D000996:Antitussive Agents; D005100:Expectorants; D010936:Plant Extracts; D012997:Solvents; C472707:caffeoylquinic acid; D011801:Quinic Acid; D000641:Ammonia; C007650:ethyl acetate; D010637:Phenolsulfonphthalein
keywords: 3,4-dicaffeoylquinic acid; 3,5-Dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid; chlorogenic acid; synergistic effect