Identification of anti-asthmatic compounds in Pericarpium citri reticulatae and evaluation of their synergistic effects.
OBJECTIVE
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 (beta(2)AR) agonistic activity using rat beta(2)AR-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 beta(2)AR 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.


CONCLUSIONS
We conclude that synephrine and stachydrine are the key components of AS that mediate asthma relief due to their synergism when used in combination.
College of Pharmaceutical Sciences, Nankai University, Tianjin, China.
Qian
Q
Shi
Ze
Z
Liu
Yang
Y
Yang
Peng
P
Geng
Yuan-yuan
YY
Zhu
Qi
Q
Zhang
Fang
F
Bai
Gang
G
Bai
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D016466:CHO Cells; D002957:Citrus / Q000737:chemistry; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification* / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010936:Plant Extracts; D011392:Proline / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000627:therapeutic use; D013578:Synephrine / Q000302:isolation & purification* / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D000470:Alkaloids; D018927:Anti-Asthmatic Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011392:Proline; D013578:Synephrine; C003342:stachydrine