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 dose-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, 1 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.
Zhou
Xin
X
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, SAR.
Leung
Pak Ho Henry
PH
Li
Na
N
Ye
Yang
Y
Zhang
Li
L
Zuo
Zhong
Z
Lin
Ge
G
D000042:Absorption / Q000187:drug effects; D000470:Alkaloids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D018938:Caco-2 Cells; D019343:Citric Acid; D003371:Cough / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D008517:Phytotherapy; D018517:Plant Roots; D041901:Stemonaceae / Q000737:chemistry*
D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D019343:Citric Acid; C034243:tuberostemonine