Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy
| Autor: | Louis R. Barrows, Teatulohi Matainaho, Prem P. Rai, Erica C. Larson, Chris D. Pond, Pius Piskaut, Michael R. Franklin, John G. Lamb, Laura B. Hathaway |
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| Rok vydání: | 2014 |
| Předmět: |
CYP2D6
Receptors Steroid Population Herb-Drug Interactions Biology Pharmacology Article Papua New Guinea Cytochrome P-450 Enzyme System Drug Discovery Cytochrome P-450 Enzyme Inhibitors Humans Enzyme inducer Medicinal plants education Pregnane X receptor education.field_of_study Plants Medicinal CYP3A4 Plant Extracts CYP1A2 Pregnane X Receptor Anti-Retroviral Agents Receptors Aryl Hydrocarbon Enzyme Induction biology.protein Microsomes Liver |
| Zdroj: | Journal of ethnopharmacology. 155(3) |
| ISSN: | 1872-7573 |
| Popis: | Ethnopharmacological relevance 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). Materials and 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. |
| Databáze: | OpenAIRE |
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