Impact of dietary plant flavonoids on 7,8‐dihydroxyflavone transepithelial transport in human intestinal Caco‐2 cells

Abstract 7,8‐dihydroxyflavone (7,8‐DHF) is a biologically active flavone with various physiological activities, including neuroprotection, anti‐inflammation, and weight loss. Previous studies have found that the efflux protein P‐glycoprotein (P‐gp) significantly affects the transepithelial transport of 7,8‐DHF in the intestine, resulting in its low oral bioavailability. Based on this, in this study, a Caco‐2 monolayer cell model was used to investigate 14 dietary plant flavonoids as potential P‐gp inhibitors, and their effects on the transepithelial transport and in vitro digestion of 7,8‐DHF were explored. The results showed that among the 14 plant flavonoids, hesperetin, epigallocatechin gallate, fisetin, kaempferol, quercetin, and isoorientin increased and the apparent permeability coefficients ( P app ) of 7,8‐DHF at AP → BL direction and lowered P app value at BL → AP direction to varying degrees, reducing the efflux ratio of 7,8‐DHF less than 1.5. In particular, kaempferol and quercetin exhibited the best effect on promoting the transepithelial transport of 7,8‐DHF, especially when used at molar concentration ratios of 1:1 and 1:2 with 7,8‐DHF. This is beneficial for improving the oral bioavailability of 7,8‐DHF. Meanwhile, 7,8‐DHF was found to maintain structural stability in simulated saliva, gastric juice, and intestinal juice, and its stability was not affected by the coexistence of quercetin and kaempferol. Overall, this study provided a theoretical basis for seeking natural and safe P‐gp inhibitors to improve the oral absorption of natural products.