Transport of parthenolide across human intestinal cells (Caco-2).
This study examined the intestinal epithelial membrane transport of the sesquiterpene lactone parthenolide, a bioactive compound present in the migraine prophylactic herb feverfew. The Caco-2 human colonic cell line was used as an in vitro model of the human intestinal mucosal barrier. The bidirectional transport (apical to basolateral and basolateral to apical) of parthenolide was investigated using Caco-2 monolayers grown on Transwell inserts. Quantitation of parthenolide was performed using high performance liquid chromatography (HPLC). Apical to basolateral and basolateral to apical permeability coefficients and percent transport were calculated and a potential bioavailability of parthenolide was determined. Sodium fluorescein was used as a marker for paracellular leakage. Parthenolide, at a concentration of 250 microM, demonstrated substantial linear transport across the monolayer. The transport parameters were not affected by the presence of MK-571, an inhibitor of multidrug resistance transporter P-glycoprotein (MRP). Upon comparison of the transport parameters of parthenolide with atenolol under identical conditions and the reported values for model compounds like mannitol and propranolol, it is concluded that parthenolide is effectively absorbed through the intestinal mucosa via a passive diffusion mechanism.
Khan
Shabana I
SI
National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. skhan@olemiss.edu
Abourashed
Ehab A
EA
Khan
Ikhlas A
IA
Walker
Larry A
LA
D001693:Biological Transport, Active / Q000187:drug effects*; D018938:Caco-2 Cells / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D008517:Phytotherapy; D012717:Sesquiterpenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D020903:Tanacetum parthenium
D012717:Sesquiterpenes; C002669:parthenolide