Evaluation of the synergistic effect of Allium sativum, Eugenia jambolana, Momordica charantia, Ocimum sanctum , and Psidium guajava on hepatic and intestinal drug metabolizing enzymes in rats.

AIMS/BACKGROUND: This study was to investigated the synergistic effect of polyherbal formulations (PHF) of Allium sativum L ., Eugenia jambolana Lam., Momordica charantia L., Ocimum sanctum Linn., and Psidium guajava L. in the inhibition/induction of hepatic and intestinal cytochrome P450 (CYPs) and Phase-II conjugated drug metabolizing enzymes (DMEs). Consumption of these herbal remedy has been extensively documented for diabetes treatment in Ayurveda.

METHODOLOGY: PHF of these five herbs was prepared, and different doses were orally administered to Sprague-Dawley rats of different groups except control group. Expression of mRNA and activity of DMEs were examined by real-time polymerase chain reaction and high performance liquid chromatography in isolated liver and intestine microsomes in PHF pretreated rats.

RESULTS: The activities of hepatic and intestinal Phase-II enzyme levels increased along with mRNA levels except CYP3A mRNA level. PHF administration increases the activity of hepatic and intestinal UDP-glucuronyltransferase and glutathione S-transferase in response to dose and time; however, the activity of hepatic sulfotransferase increased at higher doses.

CONCLUSIONS: CYPs and Phase-II conjugated enzymes levels can be modulated in dose and time dependent manner. Observations suggest that polyherbal formulation might be a possible cause of herb-drug interaction, due to changes in pharmacokinetic of crucial CYPs and Phase-II substrate drug.