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), β-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) × 10⁻⁵, (1.67 ± 0.65) × 10⁻⁵, (2.67 ± 0.30) × 10⁻⁵, (0.17 ± 0.01) × 10⁻⁵, (0.35 ± 0.02) × 10⁻⁵, (2.51 ± 0.33) × 10⁻⁵, and (2.61 ± 0.34) × 10⁻⁵ cm/s, respectively. In the concentration range of 10–200 µM, 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.

Key words

Strychnos nux‐vomica - Loganiaceae - strychnos alkaloids - intestinal permeability - Caco‐2 cell model

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