Intestinal absorption of Stemona alkaloids in a Caco-2 cell model

The intestinal absorption of neotuberostemonine and neostenine, two major bioactive alkaloids of the commonly used antitussive traditional Chinese medicine Stemona tuberosa Lour, was investigated using a Caco-2 monolayer model. Both alkaloids exhibited a high absorptive permeability which was higher for neostenine [P-app(AB) = 12.03 +/- 1.14 x 10(-6) cm/s] than for neotuberostemonine [P-app(AB) = 9.27 +/- 0.79 x 10(-6) cm/s], indicating that they are likely to be well absorbed and orally active. Furthermore, both alkaloids were identified to be the substrates of P-glycoprotein and have a transport preference from the basolateral to apical direction with efflux ratios between 2 and 3. Cyclosporin A dose-dependently inhibited the secretory permeability of these alkaloids and abolished their active efflux transport.