Wei Liu1, Yongli Wang2, Dan-dan He1, Shu-ping Li1, Yu-dan Zhu1, Bo Jiang1, Xue-mei Cheng2, Zheng--tao Wang2, Chang-hong Wang3. 1. 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. 2. 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. 3. 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.
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. OBJECTIVES: 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.
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. OBJECTIVES: 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 alkaloidsVAS, 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: Christina L Magyar; Tyler J Wall; Steven B Davies; Molly V Campbell; Haven A Barna; Sydney R Smith; Christopher J Savich; R Adam Mosey Journal: Org Biomol Chem Date: 2019-08-28 Impact factor: 3.876
Authors: Parteek Prasher; Mousmee Sharma; Meenu Mehta; Keshav R Paudel; Saurabh Satija; Dinesh K Chellappan; Harish Dureja; Gaurav Gupta; Murtaza M Tambuwala; Poonam Negi; Peter R Wich; Nicole G Hansbro; Philip M Hansbro; Kamal Dua Journal: Chem Biol Interact Date: 2020-05-04 Impact factor: 5.192