Hiroyuki Kamakura

Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities

It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research shows that Ephedra Herb also has ephedrine alkaloid-independent pharmacological actions, such as c-MET inhibitory activity. This study describes the preparation of an ephedrine alkaloids-free Ephedra Herb extract (EFE) by ion-exchange column chromatography, as well as in vitro and in vivo evaluation of its pharmacological actions and toxicity. We confirmed that EFE suppressed hepatocyte growth factor (HGF)-induced cancer cell motility by preventing both HGF-induced phosphorylation of c-Met and its tyrosine kinase activity. We also investigated the analgesic effect of EFE. Although the analgesic effect of Ephedra Herb has traditionally been attributed to pseudoephedrine, oral administration of EFE reduced formalin-induced pain in a dose-dependent manner in mice. Furthermore, we confirmed the anti-influenza virus activity of EFE by showing inhibition of MDCK cell infection in a concentration-dependent manner. All assessments of toxicity, even after repeated oral administration, suggest that EFE would be a safer alternative to Ephedra Herb. The findings described here suggest that EFE has c-Met inhibitory action, analgesic effect, and anti-influenza activity, and that it is safer than Ephedra Herb extract itself. Therefore, EFE could be a useful pharmacological agent.

Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosus

Shatavari—a famous Ayurveda materia medica used mainly as a tonic for women—is distributed in health food products all over the world. The Ayurvedic Pharmacopoeia of India identifies the botanical origin of shatavari as the tuberous root of Asparagus racemosus. We recently investigated by DNA analysis the botanical origin of shatavari products on the Japanese market. The results suggested that their botanical origin was Asparagus; however, species identification was difficult. In this study, we analyzed steroidal saponins, including those specific to this plant, in these products and confirmed their origin as A. racemosus. Next, alkaloid analyses of an authentic A. racemosus plant and these products were performed, because several papers have reported the isolation of a pyrrolo[1,2-a]azepine alkaloid, asparagamine A, from this plant. Our results suggest that neither plant material nor products contained asparagamine A. It has been pointed out that Stemona plants are sometimes mistaken for shatavari, because their tuberous roots have a similar shape to that of A. racemosus, and pyrrolo[1,2-a]azepine alkaloids are thought to be Stemona-specific. These data strongly suggest that A. racemosus does not contain asparagamine A, and that previous isolation of asparagamine A from materials claimed as originating from A. racemosus was likely caused by misidentification of Stemona plants as A. racemosus.

Isoheleproline: a new amino acid-sesquiterpene adduct from Inula helenium

A new amino acid–sesquiterpene adduct, isoheleproline (1), was isolated from the roots of Inula helenium (elecampane), together with four known sesquiterpene lactones (2–5). The planar configuration of 1 was elucidated on the basis of spectroscopic data analysis, and the relative configuration of 1 was determined by performing a detailed analysis of NOESY correlations and comparing its physicochemical data with the d- and l-proline adducts of 2 obtained by Michael addition. This is the first report of a new amino acid–sesquiterpene adduct from Inula plants.