Dihydromyricetin possesses numerous biological and pharmacological activities, and However, little data is available for its intestinal absorption mechanism. This study investigates the intestinal absorption characteristics of dihydromyricetin using Caco-2 cell transwell model. The intestinal absorption characteristics of dihydromyricetin was investigated using Caco-2 cell transwell model. Then, the effects of time (30, 60, 90, and 120 min), concentration (2, 10, and 20 mu M), temperature (37 or 4 degrees C), paracellular pathways, and efflux transporters inhibitors (verapamil, cyclosporin A, MK-571, and reserpine) on transport of dihydromyricetin were investigated. The Papp values from BL-AP of dihydromyricetin are much higher than the AP-BL permeability. The results indicated that the intestinal transport of dihydromyricetin was a time-and concentration-dependent active transport. Opening of cell junctions brings little influence in dihydromyricetin permeability in both directions, which indicated that the paracellular pathway was not involved in transport of dihydromyricetin. Decrease in the Papp(BL-AP) at 4 degrees C with respect to the Papp(BL-AP) at 37 degrees C indicate that the efflux of dihydromyricetin was energy dependent transport. Both verapamil and cyclosporin A could increase the Papp(AP-BL) and decrease the Papp(BL-AP) value. However, MK571 or reserpine have no obvious effects on the transport of dihydromyricetin. These results indicated that dihydromyricetin might be a substrate of P-gp, and while not a substrate of BCRP and MRP2. P-gp was involved in transport of dihydromyricetin, which hindered the absorption of dihydromyricetin in intestine, and drug-drug interaction might be occurred when dihydromyricetin was co-administrated with P-gp inhibitors.
[1]Shanghai Univ TCM, Peoples Hosp 7, Dept Endocrinol, Shanghai 200137, Peoples R China.
[2]Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pharm, Shanghai 200438, Peoples R China.
(8.0+极速模式)