Transport mechanisms of flavanone aglycones across Caco-2 cell monolayers and artificial PAMPA membranes
Article first published online: 10 NOV 2011
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society
Journal of Pharmacy and Pharmacology
Volume 64, Issue 1, pages 52–60, January 2012
How to Cite
Kobayashi, S., Nagai, T., Konishi, Y., Tanabe, S., Morimoto, K. and Ogihara, T. (2012), Transport mechanisms of flavanone aglycones across Caco-2 cell monolayers and artificial PAMPA membranes. Journal of Pharmacy and Pharmacology, 64: 52–60. doi: 10.1111/j.2042-7158.2011.01374.x
- Issue published online: 8 DEC 2011
- Article first published online: 10 NOV 2011
- Received April 19, 2011; Accepted September 22, 2011
- pH-partition hypothesis
Objectives We recently reported that flavanone aglycones (hesperetin, naringenin and eriodictyol) are efficiently absorbed via proton-coupled active transport, in addition to transcellular passive diffusion, in Caco-2 cells. Here, we aimed to evaluate in detail the absorption mechanisms of these flavanones, as well as homoeriodictyol and sakuranetin.
Methods We evaluated the absorption mechanisms of the above compounds by means of in vitro studies in Caco-2 cells in parallel with an artificial membrane permeation assay (PAMPA) under pH-gradient and iso-pH conditions.
Key findings Comparison of the permeability characteristics of flavanones in Caco-2 cells and in PAMPA under these conditions, as well as a consideration of the physicochemical properties, indicated that hesperetin, naringenin, eriodictyol and homoeriodictyol were efficiently transported by passive diffusion according to the pH-partition hypothesis, except in the case of sakuranetin. However, transport of all flavanones were remarkably temperature-dependent, and was significantly reduced when Caco-2 cells were treated with amino acid-modifying reagents.
Conclusions Our data confirm that both passive diffusion and an active transport mechanism contribute to flavanone absorption through human intestinal epithelium.