Evaluation of the potential effect of , , , , and on intestinal p-glycoprotein in rats.

AIMS/BACKGROUND: This study was evaluated synergistic effect of a polyherbal formulation (PHF) of L., Lam., L., Linn., and L. on p-glycoprotein (Pgp) of intestine. These five herbs were traditionally used for diabetes. These herbs are commonly present in Ayurvedic product as antidiabetics in India.

MATERIALS AND METHODS

PHF was prepared by five indigenous herbs. Different doses (50, 100 and 200 mg/kg/day) of were orally administered to Sprague-Dawley rats of different groups for multiple weeks except control groups. Alteration in Pgp expression was evaluated by real-time-polymerase chain reaction and western blotting while modulation in activity of Pgp was evaluated using rhodamine 123 (Rh123) as transport substrate by absorption and everted gut sac method.

RESULTS

In PHF, pretreated group received 50, 100 and 200 mg/kg/day for 7 days, mRNA level decreased by 1.75, 2.45 and 2.37-fold, respectively, as compared to control. Similarly, when PHF at dose of 100 mg/kg/day was given consequently for 4 weeks, maximum decrease in Pgp expression level was observed only after 1 week and further increase in the treatment duration did not produce significant decrease compared to the 1 week treatment. Pgp mediated transport of Rh123 was significantly decreased with everted gut sac prepared from PHF pretreated rats (1 week) compared to those prepared from vehicle treated rats.

CONCLUSIONS

We report that PHF pretreatment downregulated the expression of intestinal Pgp and this downregulated intestinal Pgp would result in decreased functional activity. In addition, this downregulated Pgp expression might affect the bioavailability of antidiabetic Pgp substrate drugs.