Oral Absorption and Antitussive Activity of Tuberostemonine Alkaloids from the Roots of Stemona tuberosa

The intestinal absorption of four stereoisomers of tuberostemonine-type alkaloids, neotuberostemonine (1), tuberostemonine (2), tuberostemonine H (3), and tuberostemonine J (4), isolated from the antitussive Chinese medicinal herb Radix Stemonae, and the in vivo antitussive activity of alkaloids 1, 2 and 3 were investigated in the current study. All three alkaloids exhibited close-dependent inhibitory effects on citric acid-induced cough in guinea pigs after intraperitoneal administration. Alkaloid 2 had the same potency via both oral and intraperitoneal dosing, I exhibited significantly lower oral activity than that following intraperitoneal application, while 3 did not show oral activity. Alkaloid 4 demonstrated a moderate permeability in Caco-2 monolayer cells while alkaloids 1, 2 and 3 exhibited relatively higher intestinal permeabilities, indicating that all four alkaloids tested had reasonable oral absorption.