Evaluation of the potential effect ofAllium sativum,Momordica charantia,Eugenia jambolana,Ocimum sanctum, andPsidium guajavaon intestinal p-glycoprotein in rats.
OBJECTIVE
This study was evaluated synergistic effect of a polyherbal formulation (PHF) ofAllium sativumL.,Eugenia jambolanaLam.,Momordica charantiaL.,Ocimum sanctumLinn., andPsidium guajavaL. 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.


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 byin-situabsorption 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 1stweek 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.
Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India; Department of Biotechnology, Dr. APJ Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India.
Devendra
D
Kumar
Center of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India.
Neerja
N
Trivedi
Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India.
Rakesh K
RK
Dixit
Everted-sac; herb-drug interaction; p-glycoprotein; polymerase chain reaction; western blot