Structural classification and biological activities of Stemona alkaloids

Stemona alkaloids represent a unique class of natural products exclusively isolated from the monocotyledonous family Stemonaceae comprising three genera mainly distributed in southeast Asia. Structurally the alkaloids are characterised by a pyrrolo[1,2- a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings. Based on biosynthetic considerations and their various distribution the present review describes 82 Stemona alkaloids grouped into three skeletal types. Due to different carbon chains attached to C-9 of the pyrroloazepine nucleus they were classified into stichoneurine-, protostemonine- and croomine-type alkaloids. The genera Croomia and Stichoneuron only accumulate croomine or stichoneurine derivatives, respectively, whereas the genus Stemona produces all three types of alkaloids. However, species-specific accumulation trends towards certain structural types represent valuable chemosystematic criteria. Bioassays with larvae of Spodoptera littoralis exhibited very high insect toxicity for the roots of Stemona species containing certain protostemonine derivatives, especially didehydrostemofoline, whereas those with dominating stichoneurine or croomine derivatives showed low toxicity but sometimes remarkable repellence due to an accumulation of tuberostemonine. Tuberostemonine also showed effects on the motility of helminth worms and reduced the excitatory transmission at the crayfish neuromuscular junction. Significant antitussive activity was shown for the stereoisomeric neotuberostemonine in guinea-pig after cough induction by citric acid aerosol stimulation. Studies on structure-activity relationship with seven related compounds revealed that the saturated tricyclic pyrrolobenzazepine nucleus of tuberostemonines is the prerequisite for antitussive activity.

Radix Stemonae, first recorded in the herbal 'Additional Records of Famous Physicians' (Mingyi Bielu), has been widely used as an oral anti-tussive agent in traditional Chinese medicine (TCM) for thousands of years in China. Current analysis methods are usually time-consuming and inaccurate. The aim of this study was to develop a more rapid and sensitive method to detect the active compounds in Radix Stemonae. A rapid, sensitive and selective ultra-performance liquid chromatography-high-resolution mass spectrometric (UPLC-HDMS) method with automated data analysis software MetaboLynx(TM) was developed for analysis and identification of the bioactive components and their metabolites in rat plasma following oral administration of Radix Stemonae extract. Twenty-nine compounds in the Radix Stemonae extract and 47 compounds in the rat plasma samples were detected in the MS(E) mode in a single injection within 21 min. Among the compounds detected, 23 were identified in vitro and 42 were identified in rat plasma, either by comparing the retention time and mass spectrometry data with those of reference compounds or by mass spectrometry analysis and retrieving the reference literature. It is concluded that the screening capability of MetaboLynx(TM), together with the utilisation of MS(E) in structural elucidation, can facilitate a rapid and comprehensive detection and effective structural characterisation of Stemona alkaloids in Radix Stemonae extract, which could be applied to other Chinese medicine. The results provide helpful chemical information of Radix Stemonae extract for further pharmacology and active mechanism research. Copyright © 2012 John Wiley & Sons, Ltd.