Enhanced in-vitro bioavailability of curcumin, lutein and isoflavones through interaction with spearmint (Mentha spicata) via its bioactive component (R)-(−)-carvone

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.