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

Abstract

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.