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

Abstract

Background: Flavonoid compounds are one kind of 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, the 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'''-p-coumaroylspinosin (6-CS) and 6'''-feruloylspinosin (6-FS). Results: The results of the bidirectional transport assay showed that the six flavonoids have 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 was energy-dependent monocarboxylate transporter (MCT)-mediated active transport. In particular, the para-cellular pathway also participated in the transport of IV, ST, IVG and S. Furthermore, the efflux process of six flavonoids was mediated by P-glycoprotein (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.