P-glycoprotein mediated efflux in Caco-2 cell monolayers: The influence of herbals on digoxin transport

Oga, Enoche Florence orcid iconORCID: 0000-0002-2661-0574, Sekine, Shuichi, Shitara, Yoshihisa and Horie, Toshiharu (2012) P-glycoprotein mediated efflux in Caco-2 cell monolayers: The influence of herbals on digoxin transport. Journal of Ethnopharmacology, 144 (3). pp. 612-617. ISSN 03788741

[thumbnail of Version of Record] PDF (Version of Record) - Published Version
Restricted to Repository staff only
Available under License Creative Commons Attribution Non-commercial No Derivatives.


Official URL: http://dx.doi.org/10.1016/j.jep.2012.10.001


Several herbal medicines are concomitantly used with conventional medicines with a resultant increase in the recognition of herb-drug interactions. The phytomedicines Vernonia amygdalina Delile (VA), family Asteraceae; Azadiractha indica A. Juss (NL), family Meliaceae; Morinda lucida Benth (MLB), family Rubiaceae; Cymbopogon citratus Stapf (LG), family Poaceae; Curcuma longa L. (CUR), family Zingiberaceae; Carica papaya L. (CP), family Caricaceae and Tapinanthus sessilifolius Blume (ML), family Loranthaceae are used in African traditional medicine for the treatment of malaria. They are also used in several regions world over in managing other ailments like cancer and diabetes. This study investigated their interaction with digoxin (DIG) with a view to predict the potential of P-glycoprotein (p-gp) mediated drug-herb interactions occurring with p-gp substrate drugs.
To assess p-gp mediated transport and inhibition, bidirectional transport studies were carried out on Caco-2 cell monolayers using digoxin (DIG) as a model p-gp substrate. Cell functionality was demonstrated using the determinations of transepithelial electric resistance (TEER), cell cytotoxicity testing utilizing the MTT assay as well as the inclusion of inhibition controls.
Under the conditions of this study, extracts of ML, VA and CP showed significant inhibition to (3)H-Digoxin basolateral-to-apical (B-A) transport at 0.02-20mg/mL; the concentrations examined. Their apical-to-basolateral (A-B) transport was further investigated. Increases in the mean A-B transport and significant decreases in the B-A transport and efflux ratio values were observed. The apparent permeability coefficient and efflux ratio were computed providing an estimate of drug absorption.
The findings show that extracts of ML, VA and CP significantly inhibit p-gp in vitro and interactions with conventional p-gp substrate drugs are likely to occur on co-administration which may result in altered therapeutic outcomes.

Repository Staff Only: item control page