Identification of anti-asthmatic compounds in Pericarpium citri reticulatae and evaluation of their synergistic effects  

作　　者：Qian SHI Ze LIU Yang YANG Peng GENG Yuan-yuan ZHU Qi ZHANG Fang BAI Gang BAI 

机构地区：[1]College of Pharmaceutical Sciences, Nankai University, Tianjin 300071, China [2]College of Life Sciences, Nankai University, Tianjin 300071, China [3]College for Basic Medical Science, Tianjin Medical University, Tianjin 300070, China

出　　处：《Acta Pharmacologica Sinica》2009年第5期567-575,共9页中国药理学报（英文版）

基　　金：Acknowledgements The work was supported in part by the National High Technology Research and Development Program of China （863 Program, No 2006AA020502）, and Grant No 07JCZDJCOS000 from the Natural Science Foundation of Tianjin, China.

摘　　要：Aim： To investigate the anti-asthmatic mechanisms of the traditional Chinese medicine Pericarpium citri reticulatae （PCR）. Methods： The alkaloid section （AS） of PCR was extracted using an ion exchange resin, separated, and purified into different fractions by semi-preparative HPLC. These fractions were screened for beta2-adrenergic receptor （β2AR） agonistic activity using rat β2AR-transfected CHO-CRE-EGFP cells. AS and its isolated components were characterized by ultra-performance liquid chromatography/quadrupole time-of-flight MS （UPLC/Q-Tof MS） and were evaluated for their spasmolytic and antitussive activities both in vitro and in vivo in a guinea pig model. Results： We demonstrated that the AS component responsible for activating β2AR signaling was synephrine. Both AS and synephrine showed significant spasmolytic effects on acetylcholine chloride （ACh）-induced contractions in isolated guinea pig trachea, and they protected against histamine-induced experimental asthma by prolonging the latent period. We further identified stachydrine as the antitussive component that could significantly reduce citric acid-induced coughing. The combination of these two bioactive compounds had a more potent spasmolytic activity in comparison with the single use of synephrine or stachydrine. Conclusion： We conclude that synephrine and stachydrine are the key components of AS that mediate asthma relief due to their synergism when used in combination.Aim： To investigate the anti-asthmatic mechanisms of the traditional Chinese medicine Pericarpium citri reticulatae （PCR）. Methods： The alkaloid section （AS） of PCR was extracted using an ion exchange resin, separated, and purified into different fractions by semi-preparative HPLC. These fractions were screened for beta2-adrenergic receptor （β2AR） agonistic activity using rat β2AR-transfected CHO-CRE-EGFP cells. AS and its isolated components were characterized by ultra-performance liquid chromatography/quadrupole time-of-flight MS （UPLC/Q-Tof MS） and were evaluated for their spasmolytic and antitussive activities both in vitro and in vivo in a guinea pig model. Results： We demonstrated that the AS component responsible for activating β2AR signaling was synephrine. Both AS and synephrine showed significant spasmolytic effects on acetylcholine chloride （ACh）-induced contractions in isolated guinea pig trachea, and they protected against histamine-induced experimental asthma by prolonging the latent period. We further identified stachydrine as the antitussive component that could significantly reduce citric acid-induced coughing. The combination of these two bioactive compounds had a more potent spasmolytic activity in comparison with the single use of synephrine or stachydrine. Conclusion： We conclude that synephrine and stachydrine are the key components of AS that mediate asthma relief due to their synergism when used in combination.

关 键 词：Pericarpium citri reticulatae （PCR） asthma beta2-adrenergic receptor （β2AR） agonists BRONCHODILATOR ANTITUSSIVE SYNEPHRINE stachydrine 

分 类 号：R284[医药卫生—中药学] R974.3[医药卫生—中医学]