Citrus, Milk Thistle, and Propolis Extracts Improved the Intestinal Permeability of Curcuminoids from Turmeric Extract? an In Silico and In Vitro Permeability Caco-2 Cells Approach

Curcumin has been traditionally used in food recipes for biological health benefits. However, these properties are compromised due to its very low bioavailability. Thus, this work assessed the impact of using natural potential bioenhancers to improve intestinal permeability and understanding the interaction of flavonoids with curcuminoids through molecular dynamic simulation. The intestinal permeability (Papp) was measured on the human colon carcinoma cell line (Caco-2). The Papp values measured on Caco-2 cell monolayers provided information regarding the increased permeability of curcumin across the intestinal barrier specially caused by the presence of citrus (100.45%), and milk thistle extracts (81.70%) at level +1 showed the higher Papp increase (%) compared to level 0. With respect to the soft standardized green propolis EPP-AF extract, the Papp increase was higher at level 0 (26.34%). Molecular dynamic (MD) simulations of curcumin with naringin and silybin B confirmed this increase of permeability of curcumin at higher concentrations through non-covalent interactions. These results suggest the prominent importance of the association of natural flavonoids as bioenhancers to increase curcumin bioavailability and health benefits.