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
Authors
Devendra Kumar
Department of Pharmacology and Therapeutics, King George’s Medical University, Lucknow, Uttar Pradesh, India
Neerja Trivedi
Center of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India
Rakesh Dixit
Department of Pharmacology and Therapeutics, King George’s Medical University, Lucknow, Uttar Pradesh, India
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.
KEY WORDS: Cytochrome P450, herb-drug interaction, microsomes, sulfotransferase, UDP-glucuronyltransferase
Author Biography
Devendra Kumar, Department of Pharmacology and Therapeutics, King George’s Medical University, Lucknow, Uttar Pradesh, India
Department of Biotechnology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow, Uttar Pradesh, India
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