Mechanism of the Intestinal Absorption of Six Flavonoids from Zizyphi Spinosi Semen Across Caco-2 Cell Monolayer Model.

BACKGROUND Flavonoid compounds are one kind active ingredients isolated from a traditional Chinese herb Zizyphi Spinosae Semen (ZSS). Studies have shown that ZSS flavonoids have significant antioxidant effects. METHODS In this study, Caco-2 cell monolayer model was constructed to investigate the intestinal absorption characteristics and mechanism of Isovitexin (IV), Swertisin (ST), Isovitexin-2''-O-β-D-glucopyranoside (IVG), Spinosin (S), 6'''-pcoumaroylspinosin (6-CS) and 6'''-feruloylspinosin (6-FS). RESULTS The results of bidirectional transport assay showed that the six flavonoids have a good intestinal absorption in a near-neutral and 37 °C environment, and the absorbability in descending order was 6-FS＞6-CS＞IVG＞S＞IV＞ST. The results of carrier inhibition experiments and transport kinetics indicated that the absorption mechanism of six flavonoids were energy-dependent monocarboxylate transporter (MCT)-mediated active transport. In particular, para-cellular pathway also participated in the transport of IV, ST, IVG and S. Furthermore, the efflux process of six flavonoids was mediated by Pglycoprotein (P-gp) and multidrug resistance protein (MRP), which may result in a decrease of bioavailability. CONCLUSION Our findings provide significant information for revealing the relationship between the intestinal absorption mechanism of flavonoids and its structure as well as laying a basis for the research of flavonoid preparations.