| Bulbus Fritillariae (Beimu) is derived from the bulbs of Fritillaria species in the family Liliaceae. It is one of the most commonly used antitussive and expectorant drugs in traditional Chinese medicine (TCM). However, like numerous TCM herbs used in the Chinese community, a lack of scientific evidence for the usefulness of Beimu prevents the acceptance of the therapeutic use of this TCM herb by the Western society. The present study aims to systematically investigate the chemical and pharmacological bases of Beimu and to provide scientific evidence to support the rationale for the use of this well-known TCM herb.;Firstly, three novel analytical methods, namely gas chromatography with pre-column derivatization, direct gas chromatography, and direct high performance liquid chromatography (HPLC) with evaporative laser scattering detector (ELSD), have been developed to examine the Fritillaria alkaloids, the major pharmacologically active components in Beimu. Twenty-four different Fritillaria species, which are the sources for different Beimu herbs, were tested. The results demonstrated that the major active Fritillaria alkaloids present in different Beimu herbs vary in both quantity and type, and thus such chemical variations may lead to different therapeutic outcomes for different Beimu herbs. Furthermore, the chemical variations in Beimu herbs were shown to be related to the geographical locations of the plants.;In the pharmacological studies, five major Fritillaria alkaloids namely, imperialine, verticine, verticinone, ebeiedine, and puqietinone, were investigated for their relaxation effect on isolated rat tracheal and bronchial rings. All five alkaloids tested exhibited relaxation effect on carbachol pre-contracted rat trachea and bronchus, with a rank order of potency: imperialine > verticine ≥ verticinone > ebeiedine > puqietinone. These results demonstrated for the first time that the tracheobronchial relaxation effects caused by these three alkaloids: imperialine, verticine and verticinone, were due to the competitive antagonism of muscarinic receptors. In addition, the relaxation effect of Fritillaria alkaloids was also shown to involve the inhibition of the influx of extracellular calcium. (Abstract shortened by UMI.). |
