Effect of P-glycoprotein on the transmembrane absorption and metabolism of quercitrin on Caco-2 cells / 国际药学研究杂志

ABSTRACT

Objective To explore the role of P-glycoprotein(P-gp)on cellular uptake and metabolism in the transmembrane transport of quercitrin.Methods Caco-2 cell monolayer and P-gp inhibitor Cyclosporin A(CysA)were used in the study.Quercitrin, quercetin,isorhamnetin and tamarixetin were determined by LC-MS to study cellular uptake and metabolism of quercitrin on Caco-2 cells.Results Uptake of quercitrin by Caco-2 cells:in different concentration groups of quercitrin coincubating with and without Cy?sA,intracellular accumulation presented the following characteristics:the amount of quercitrin first rose,reached the peak in 60 min and then declined to a steady-state in 120 min.And meanwhile there were significant differences between the two different processing groups incubating with and without CysA(P<0.05);quercetin was detected in all groups(3.0,9.0 and 27.0 mg/L).But in the higher concentration groups incubating with and without CysA,the intracellular quercetin presented a characteristics similar to its original glycosides and showed a significant difference(P<0.05),while the other groups showed no concentration-and time-dependence.At the same time,isorhamnetin and tamarixetin were detected in two higher concentration groups incubating with and without CysA, which showed the trend similar to the original glycosides but no significant difference was obtained between the two processing groups(P>0.05).Isorhamnetin and tamarixetin were not detected in the low and middle concentration groups.Transmembrane transport:on the basal lateral of all groups,the content of the quercitrin in 150 min incubation time showed a trend of continuous rise,and there was no significant difference between the two processing groups.Quercetin,isorhamnetin and tamarixetin were not detected.Conclu?sion Intact quercitrin could be absorbed into the Caco-2 cells and transported across the Caco-2 cell monolayer,and suffered a series of further metabolism in the Caco-2 cells and the basal side of Caco-2 cell monolayer,leading to different characteristics between intra?cellular accumulation and transmembrane transport.P-gp reduces the transmembrane transport of quercitrin by its efflux function,but did not involved in quercitrin metabolism.