Antitussive alkaloids of Stemona tuberosa

Cough is an airway defensive reflex, which is responsible for keeping the airway free of obstruction and harmful substances. As the commonest symptom for which medical advices is sought, enormous costs are spent on cough treatments. Regretfully, currently used antitussives are less than satisfactory due to their low potency or obvious side effects. So it is necessary to continue developing new and better antitussives.; The Chinese herb Radix Stemonae (Baibu) has long been used as an antitussive in Chinese medicine for some two thousand years. Its source materials, according to the Pharmacopoeia of the People's Republic of China (PRC Pharmacopoeia), come from the tuberous roots of three Stemona species, namely, S. japonica (Blume) Miq., S. sessilifolia (Miq.) Miq. and S. tuberosa Lour. However, hardly any experimental study is available to document their antitussive functions. Chung et al. (2003) reported that the antitussive components of S. tuberosa were neotuberostemonine and related stenine type Stemona alkaloids. And the antitussive potency of neotuberostemonine through intraperitoneal administration was reported to be comparable to codeine but not involving opioid receptors. In continuation with the study of the antitussive properties of the herb, it was found that total alkaloids of different samples of the herb appeared to vary in chemical profiles, whereas neotuberostemonine was found in only a few samples.; In order to determine if the different chemical profiles of Stemona total alkaloids were the result of species difference or variations within the same species, the three Stemona species registered in the PRC Pharmacopoeia were collected from different areas in China. They were planted to flowering in our greenhouse and authenticated by both reproductive and vegetative characters. Microscopic examination on these authentic species showed that tuberous roots of S. tuberosa differed by epidermal cells with smooth outer surface and fibers in the cortex and pith from those of S. japonica and S. sessilifolia. The chemical profiles of authentic samples were analyzed on a HPLC-ELSD system. The results indicated that species-specific differences were present in the HPLC profiles of the three Stemona species. Within S. tuberosa, the chemical profiles of different samples were found to be very variable and they could be roughly divided into four types in the tested samples. Neotuberostemonine was present in one of the four types of S. tuberosa. Since antitussive effects of neotuberostemonine were demonstrated by Chung et al. (2003), it became necessary to determine if the samples containing alkaloids other than neotuberostemonine had antitussive properties.; Bioassays of total alkaloids of S. tuberosa samples representing the four types of chemical profiles were conducted on guinea pigs using citric acid aerosol for inducing cough. These results demonstrated their antitussive properties and thus suggested the possibility of other antitussive alkaloids than neotuberostemonine in S. tuberosa. So it became necessary to identify the major components in the samples of S. tuberosa representing the four types of chemical profiles.; The major components of S. tuberosa including stemoninine, croomine and neotuberostemonine were isolated and determined by spectroscopic methods. It was the first time to isolate croomine from Stemona species, lending support to retaining the two genera Stemona and Croomina in the family Stemonaceae according to chemotaxonomy. Tuberostemonine, another major component of S. tuberosa was also isolated and determined in our team. Neotuberostemonine and tuberostemonine were two isomers but mutually exclusive in our tested samples. Moreover, these major components of S. tuberosa belonged to three types in molecular structure. Stemoninine was stemonamide type, croomine tuberostemospironine type and both neotuberostemonine and tuberostemonine stenine type. These results suggested that antitussive effects...