Effects of phyllanthin and hypophyllanthin on functioning of P-glycoprotein and multidrug resistance protein 2 in caco-2cells

Abstract

The purpose of this study was to investigate and compare the effects of phyllanthin and hypophyllanthin on the function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), using the in vitro model of the Caco-2 cells. Furthermore, prolonged exposure to phyllanthin and hypophyllanthin on function of P-gp was determined. The activities of P-gp and MRP2 were assessed by measuring the intracellular accumulation of their specific substrate. Under the conditions used in this study, the Caco-2 cells cultured for 21 days expressed the function of both Pgp and MRP2 efflux pumps. The results demonstrated that hypophyllanthin was able to inhibit the P-gp function in comparable potency with phyllanthin, but the inhibitory effects of both compounds against MRP2 were not observed. By varying the treatment conditions, the inhibitory action of both compounds against P-gp function could be loss. This finding suggested the reversibility of the inhibitory effect of these two compounds. Nevertheless, prolonged exposure of the Caco-2 cells to either phyllanthin or hypophyllanthin for 2 or 7 days had no significant effects on the variation of P-gp function. Hence, it was possible that phyllanthin and hypophyllanthin might be able to cause problems regarding P-gp-mediated drug interactions through the direct inhibition of this efflux pump.