title: Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L.
abstract: BACKGROUND
  The aerial parts of Peganum harmala L. (APP) is a well-known and effective herbal medicine in China, and has been commonly used for treating various ailments, including cough and asthma.
  
  
  OBJECTIVE
  To evaluate the antitussive, expectorant, and bronchodilating effects of the quinazoline alkaloids (±)-vasicine (VAS), deoxyvasicine (DVAS) (both isolated from the alkaloid fraction of APP) and (±)-vasicinone (VAO) (synthesized from VAS).
  
  
  METHODS
  The three quinazoline alkaloids were tested as antitussive on cough models in mice and guinea pigs. VAO was synthesized from VAS via the oxidation of hydrogen peroxide. VAS, VAO, and DVAS were orally administered at dosages of 5, 15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated by using a bronchoconstrictive induced by acetylcholine chloride and histamine in guinea pigs.
  
  
  RESULTS
  In antitussive tests, VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals. At the highest doses tested (45 mg/kg), they showed antitussive activities similar to codeine phosphate (30 mg/kg) in mice and guinea pigs. Expectorant evaluation showed that VAS, VAO, and DVAS could significantly increase phenol red secretion in mice by 0.54-, 0.79- and 0.97-fold, by 0.60-, 0.99-, and 1.06-fold, and by 0.46-, 0.73-, and 0.96-fold, respectively, at dosages of 5, 15, and 45 mg/kg compared with the control (0.5% CMC-Na, 20 ml/kg). Ammonium chloride at 1500 mg/kg increased phenol red secretion in mice by 0.97-fold compared with the control. Bronchodilation tests showed that VAS, VAO, and DVAS prolonged the pre-convulsive time for 28.59%, 57.21%, and 29.66%, respectively, at a dose of 45 mg/kg in guinea pigs, whereas aminophylline prolonged the pre-convulsive time by 46.98% compared with pretreatment.
  
  
  CONCLUSIONS
  Quinazoline alkaloids VAS, VAO, and DVAS have significant antitussive, expectorant, and bronchodilating activities. VAS, VAO, and DVAS are the active ingredients in APP, which can be used to treat respiratory disease.
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: He
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
authors.forename: Shu-ping
authors.initials: SP
authors.lastname: Li
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
authors.forename: Yu-dan
authors.initials: YD
authors.lastname: Zhu
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Cheng
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China.
authors.forename: Zheng--tao
authors.initials: Z-
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China. Electronic address: wchcxm@hotmail.com.
authors.forename: Chang-hong
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*; D003371:Cough / Q000188:drug therapy; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005100:Expectorants / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D015394:Molecular Structure; D032443:Peganum / Q000737:chemistry*; D035261:Plant Components, Aerial / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011799:Quinazolines / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000996:Antitussive Agents; D001993:Bronchodilator Agents; D004365:Drugs, Chinese Herbal; D005100:Expectorants; D011799:Quinazolines; C019592:vasicine; C052548:vasicinone
keywords: Antitussive; Bronchodilating; Expectorant; Peganum harmala L; Quinazoline