Acta Pharmacologica Sinica (2009) 30: 567-575; doi: 10.1038/aps.2009.36; published online 13th April 2009

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.

Keywords: Pericarpium citri reticulatae (PCR); asthma; beta2-adrenergic receptor (β₂AR) agonists; bronchodilator; antitussive; synephrine; stachydrine