Inhibitory effect of fruit extracts on P-glycoproteinrelated efflux carriers: an in-vitro screening

ABSTRACT In this study, standardized food extracts were screened for their possible inhibitory effect on the P‐glycoprotein (P‐gp)‐mediated efflux of 3H‐ciclosporin A (CsA) using the in‐vitro Caco‐2 model. CsA is commonly used as a substrate for P‐gp‐related efflux carriers and is characterized by a polarity in transport, the absorptive transport being much lower than the secretory transport (polarity factor: PF ˜ 7). Of the 68 tested, nine extracts showed a decreased efflux of CsA (< 75% of the reference value) and were retained for further experiments on the bidirectional transport of CsA across Caco‐2 monolayers. Results of these experiments showed that strawberry, orange, apricot and mint extract exert an inhibitory effect on intestinal P‐gp‐related functionality (PF < 4.2). The effect of apricot extract was also studied on the bidirectional transport of talinolol, a specific P‐gp substrate; inclusion of 1 %, v/v, in the apical compartment of Caco‐2 monolayers resulted in a significantly reduced polarity in the transport of talinolol (PF reference = 15.5; PF in the presence of apricot extract = 2.5). This study suggests that co‐administration of fruit extracts might be a conceptually safe and useful strategy to enhance the intestinal absorption of P‐gp substrates. More research is necessary to characterize the impact of this inhibition on P‐gp‐related efflux mechanisms in other absorption models (in‐vitro and in‐vivo) and to identify the compounds that are responsible for this inhibitory effect.