Intestinal absorption is intrinsically low for lipophilic micronutrients and phytochemicals. Plant extracts acting as bioavailability enhancers can complement for this deficiency by modulation of both, physicochemical and biochemical parameters, in the absorption process. However, these interactions often are limited to specific conditions and the mechanisms and potential synergisms are poorly understood. In this work, we used a human intestinal cell line to characterize the impact of extracts from C. longa (curcuma), Z. officinale (ginger) and P.nigrum (black pepper) on uptake and transport rates of the xanthophylls lutein and zeaxanthin as well as soy isoflavones measured by HPLC-DAD. We found a significant increase in the uptake of lutein in the presence of curcuma extract and enhanced isoflavone transport rates mediated by curcuma and ginger extracts. Combinations of the plant extracts did not lead to any additional increase in uptake or transport rates. By investigation of mixed micelle incorporation efficiency, we could dismiss changes in bioaccessibility as a potential enhancing mechanism in our experimental setup. We further conducted a rhodamine 123 efflux assay and discovered inhibition of P-glycoproteins by the ginger and black pepper extracts, highlighting a plausible route of action leading to increased isoflavone bioavailability.

Numerous dietary phytochemicals such as curcumin, lutein and isoflavones are associated with health beneficial activities, however their application is often limited by their low bioavailability. Therefore, bioenhancers represent a feasible approach to increase the absorption efficiency of bioactive compounds. Here, we combined uptake and transport studies in differentiated Caco-2 cells with high resolution analytics and fractionation to evaluate the impact of spearmint (Mentha spicata) on the cellular uptake of curcumin. Additionally, we utilized mechanistic studies in native and overexpressing cell systems to assess P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporter activity as well as in-silico molecular docking simulations. We found significantly elevated intracellular curcuminoid levels mediated by spearmint. Fractionation and functional assays identified (R)-(-)-carvone as a putative candidate for the biologically active compound mediating increased curcumin uptake via BCRP inhibition. Inhibition of P-gp-mediated efflux might additionally be involved. Molecular docking simulations suggest a common binding site of curcumin and (R)-(-)-carvone in BCRP. Further, spearmint significantly increased cellular uptake of lutein and transintestinal transport of isoflavones in-vitro. In summary, spearmint was identified as a novel bioenhancer for curcumin, lutein and isoflavones. Our findings suggest that spearmint increases bioavailability of a wide range of nutrients and drugs at least partially due to interference with BCRP via its active compound (R)-(-)-carvone.