Add time:08/14/2019         Source:sciencedirect.com

Araloside A is a triterpenoid saponin,which exhibits a broad spectrum of pharmacological activities, such as stimulating fibrinolysis, preventing coagulant, inhibiting renin, and decreasing blood pressure. Our previous report found that the compound exhibits a poor absolute bioavailability. However the underlying mechanisms of its absorption have not been investigated in the small intestine or in a Caco-2 cell model. In this study, the absorption mechanisms of araloside A were investigated in a Caco-2 cell monolayer and in a single-pass intestinal perfusion in situ model with Sprague-Dawley rats. The effects of basic parameters, such as compound concentration, time, temperature, paracellular pathway, different intestinal segments were analyzed, and the susceptibility of araloside A absorption process to treatment with various inhibitors, such as the P-gp inhibitor verapamil, the multidrug resistance protein2 inhibitors (MRP2) MK571 and indomethacin, the breast cancer resistance protein (BCRP) inhibitors Ko143 and reserpine, and endocytosis inhibitor chlorpromazine were assessed. It can be found that the mechanisms of intestinal absorption of araloside A may involve multiple transport pathways, such as passive diffusion, the paracellular pathway, as well as the participation of efflux transporters.

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