In vitro Tracheobronchial Relaxation of Fritillaria Alkaloids.

Abstract: Aim: Beimu (Bulbus Fritillariae) is a commonly used anti-tussive traditional Chinese herbal medicine and the major Fritillaria alkaloids in the herb are believed to be responsible for its antitussive activity. However, the detailed underlying mechanism and potency of individual Fritillaria alkaloids are still not very clear. Methods: In the present study, we investigated and compared the relaxant effect of five major Fritillaria alkaloids [imperialine (IMP), verticine (VER), verticinone (VERN), ebeiedine (EBE) and puqietinone (PUQ)] using rat isolated tracheal and bronchial preparations pre-contracted with carbachol. Results: All five Fritillaria alkaloids caused a concentration-dependent relaxation of both tracheal and bronchial preparations with the relative relaxing potency of IMP < VER ≅ VERN < EBE < PUQ. Amongst all five alkaloids tested, IMP (an isosteroidal Fritillaria alkaloid with a cis-configuration in rings D and E) was found to be the most potent; whereas PUQ (a steroidal Fritillaria alkaloid) was the least effective one. Furthermore, three Fritillaria alkaloids, namely IMP, VER and VERN (≥ 1 μmol·L⁻¹) were capable of eliciting parallel rightward shifts of the carbachol concentration-response curve, demonstrating a competitive antagonism in muscarinic pathway. In addition, the suppression of carbachol-induced contraction caused by all five isosteroidal Fritillaria alkaloids was also partly due to the inhibition of influx of calcium ions. Conclusion: The results demonstrated that the major isosteroidal Fritillaria alkaloids might be the most active constituents responsible for the anti-tussive activity of herbal Beimu with the mechanisms of competitive antagonism of muscarinic pathway and also the inhibition of influx of calcium ions. [Copyright &y& Elsevier]