title: Evaluation of the synergistic effect ofAllium sativum, Eugenia jambolana, Momordica charantia, Ocimum sanctum, andPsidium guajavaon hepatic and intestinal drug metabolizing enzymes in rats.
abstract: OBJECTIVE
  This study was to investigated the synergistic effect of polyherbal formulations (PHF) ofAllium sativum L.,Eugenia jambolanaLam.,Momordica charantiaL.,Ocimum sanctumLinn., andPsidium guajavaL. 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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Devendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Center of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Neerja
authors.initials: N
authors.lastname: Trivedi
authors.affiliation: Department of Pharmacology and Therapeutics, King George's Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Dixit
keywords: Cytochrome P450; UDP-glucuronyltransferase; herb-drug interaction; microsomes; sulfotransferase