title: Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy.
abstract: BACKGROUND
  A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs).
  
  
  METHODS
  Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates.
  
  
  RESULTS
  Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties.
  
  
  CONCLUSIONS
  We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA. Electronic address: erica.c.larson@utah.edu.
authors.forename: Erica C
authors.initials: EC
authors.lastname: Larson
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA. Electronic address: laura.hathaway@utah.edu.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Hathaway
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA. Electronic address: greg.lamb@hci.utah.edu.
authors.forename: John G
authors.initials: JG
authors.lastname: Lamb
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA. Electronic address: chris.pond@hsc.utah.edu.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Pond
authors.affiliation: School of Medicine and Health Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea. Electronic address: raipp@yahoo.com.
authors.forename: Prem P
authors.initials: PP
authors.lastname: Rai
authors.affiliation: School of Medicine and Health Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea; School of Natural and Physical Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea. Electronic address: lmatainaho@yahoo.com.
authors.forename: Teatulohi K
authors.initials: TK
authors.lastname: Matainaho
authors.affiliation: School of Natural and Physical Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea. Electronic address: piskautp@upng.ac.pg.
authors.forename: Pius
authors.initials: P
authors.lastname: Piskaut
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA; School of Medicine and Health Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea; School of Natural and Physical Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, NCD, Papua New Guinea. Electronic address: lbarrows@pharm.utah.edu.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Barrows
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 E., Salt Lake City, Utah 84112, USA. Electronic address: michael.franklin@pharm.utah.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franklin
mesh_terms: D044966:Anti-Retroviral Agents; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D041743:Herb-Drug Interactions; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010219:Papua New Guinea; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism
chemical_list: D044966:Anti-Retroviral Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D000077297:Pregnane X Receptor; D018336:Receptors, Aryl Hydrocarbon; D011987:Receptors, Steroid; D003577:Cytochrome P-450 Enzyme System
keywords: Antiretroviral therapy; Cytochrome P450s; Herb–drug interactions; Papua New Guinea; Traditional medicine Asia and Oceania