title: Intestinal permeability of antitumor alkaloids from the processed seeds of Strychnos nux-vomica in a Caco-2 cell model.
abstract: The uptake and intestinal permeability of the seven alkaloids strychnine (Str), brucine (Bru), beta-colubrine (Col), strychnine N-oxide (S-N), brucine N-oxide (B-N), pseudostrychnine (Psd), and icajine (Ica), which were isolated from the processed seeds of Strychnos nux-vomica L., were investigated in the human intestinal Caco-2 model. Determination of compounds was carried out by HPLC. The apparent permeability coefficients ( P(app)) for Str, Bru, Col, S-N, B-N, Psd, and Ica in the apical-to-basolateral direction were (3.11 +/- 0.17) x 10(-5), (1.67 +/- 0.65) x 10(-5), (2.67 +/- 0.30) x 10(-5), (0.17 +/- 0.01) x 10(-5), (0.35 +/- 0.02) x 10(-5), (2.51 +/- 0.33) x 10(-5), and (2.61 +/- 0.34) x 10(-5) cm/s, respectively. In the concentration range of 10-200 microM, Str, Bru, Col, and Psd showed substantial concentration-dependent transport across the monolayers. The transports of all seven alkaloids were linear with time and showed moderate to high permeabilities. In the presence of 2,4-dinitrophenol or sodium azide, the P(app) of Ica was reduced significantly in both the apical-to-basolateral and basolateral-to-apical directions. The dominant mechanism of the intestinal absorption for Str, Bru, Col, S-N, B-N, and Psd was passive diffusion, while it was partially ATP dependent for Ica.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs and Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Bao-Chang
authors.initials: BC
authors.lastname: Cai
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000470:Alkaloids / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D001692:Biological Transport; D018938:Caco-2 Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D010539:Permeability; D010936:Plant Extracts / Q000493:pharmacokinetics*; D012639:Seeds; D019810:Sodium Azide / Q000494:pharmacology; D031461:Strychnos nux-vomica / Q000737:chemistry*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D014475:Uncoupling Agents; D019810:Sodium Azide; D019297:2,4-Dinitrophenol