Exploring the Transmembrane Behaviors of Dietary Flavonoids under Intestinal Digestive Products of Different Lipids: Insights into the Structure–Activity Relationship In Vitro

This study aimed to investigate the transmembrane transport behavior and structure–activity relationships of various dietary flavonoids in the presence of dietary lipids derived from different sources in vitro. Results revealed that the digestion products of soybean oil (SOED) and lard (LOED) augmented the apparent permeability coefficients of most dietary flavonoids, and SOED exhibited higher transport compared with LOED. The structural properties of flavonoids and the potential interactions between fatty acids in these digestion products and flavonoids may influence the outcomes. 3D quantitative structure–activity relationship analyses revealed that incorporating small-volume groups at position 8 of the A-ring augmented the transmembrane transfer of flavonoids in the LOED system compared with the control group. By contrast, the integration of hydrophobic groups at position 5 of the A-ring and hydrogen bonding acceptor groups at position 6 of the A-ring enhanced the transmembrane transportation of flavonoids in the SOED system. Molecular dynamics simulations revealed that the SOED system may facilitate the interactions with flavonoids to form more stable and compact fatty acid–flavonoid complexes compared to the LOED system. These findings may provide valuable insights into flavonoid absorption to facilitate the development and utilization of functional foods or dietary supplements based on dietary flavonoids.