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Caco‐2 Cell methodology and inhibition of the P‐glycoprotein transport of digoxin by Aloe vera Juice
Author(s) -
Djuv Ane,
Nilsen Odd Georg
Publication year - 2008
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2536
Subject(s) - aloe vera , digoxin , caco 2 , pharmacognosy , traditional medicine , p glycoprotein , glycoprotein , chemistry , pharmacology , food science , in vitro , biochemistry , biological activity , medicine , antibiotics , multiple drug resistance , heart failure
The aims of this study were to carry out a thorough quality control setup for essential Caco‐2 cell characteristics in P‐glycoprotein (P‐gp) inhibition studies and to explore if Aloe vera juice (AVJ) inhibits the bidirectional transport of the P‐gp substrate digoxin (30 n m ). Seven AVJ concentrations (0.00001‐1.0 mg/mL), anticipated to cover a clinically relevant range, were tested and digoxin apparent permeability coefficients ( Papp ), net Papp values ( Papp Net ) and net flux values ( J Net ) were calculated. Relevant validation parameters for P‐gp inhibition studies in Caco‐2 cells are suggested to include, as a minimum, an assay linearity test with and without a known P‐gp inhibitor, cell cytotoxicity testing (MTT‐test) for substrates and inhibitors, and cell integrity testing by TEER and mannitol transport measurements. The question is also raised whether a minimum effect of a reference P‐gp inhibitor as verapamil should be demanded. Cell cytotoxicity was seen for digoxin at concentrations ≥3 µ m and for AVJ at 10 mg/mL. AVJ did not inhibit the P‐gp transport of digoxin in any of the concentrations tested. This indicates that AVJ is no inhibitor of the P‐gp mediated transport of digoxin in vitro if AVJ is present in clinically relevant concentrations. Copyright © 2008 John Wiley & Sons, Ltd.