THE IN VITRO AND EX VIVO EFFECT OF PHYLLANTHUS NIRURI METHANOL EXTRACT ON HEPATIC UDP-GLUCURONYLTRANSFERASE ENZYME ACTIVITY IN STZ-INDUCED DIABETIC SPRAGUE DAWLEY RATS

摘要

Objective: The aim of the study was to investigate the in vitro and ex vivo (acute and sub-chronic doses) effect of Phyllanthus niruri methanol extract (PNME) on the microsomal UDP-glucuronyltransferase (UGT) enzyme activity in streptozotocin (STZ)-induced diabetic young female Sprague Dawley (SD) rats. Methods: Young female SD rats were induced type I diabetes mellitus using STZ (60 mg/kg i. v.). The in vitro study was performed on a microsomal fraction of diabetic rat livers using PNME in doses of (0.01 μg, 1 μg and 10 μg)/ml. While ex vivo studies were performed on the microsomal fraction of diabetic rats using PNME in doses of 500, 1000, 2000 and 5000 mg/kg p. o. for acute ex vivo study (one-day treatment) and 100, 500 and 2000 mg/kg/day p. o. for sub-chronic one (daily dose for two weeks). p -nitrophenol ( p -NP), was used as a marker substrate for UGT enzyme activity and analyzed using the spectrophotometer to determine UGT enzyme activity. Results: The in vitro result showed that, there is no significant effect of the three concentrations of PNME versus control on UGT activity in the microsomal fraction of diabetic young female SD rat livers, while for ex vivo study, the result showed that UGT activity in the microsomal fraction of diabetic young female SD rats significantly and dose-independently increased at doses 1000, 2000 and 5000 mg/kg p. o in acute study (all p <0.05 vs control). However, no significant effect of PNME has been seen in the three doses used in the sub-chronic study. Conclusion: The three different concentrations of PNME have no significant effect as compared to control on UGT activity in the in vitro study. However, ex vivo study showed significant and dose-independent increased in UGT activity at doses 1000, 2000, and 5000 mg/kg p. o in acute study (all P<0.01 vs control), but no significant effect on sub-chronic study. Keywords: Phyllanthus niruri , UGT, Diabetic rats, Microsomal liver fraction, p -NP.