Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy

Abstract

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.

Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea

“…[ 14 , 15 ] Some of these issues such as stigma, side effects and forgetting are also common in the developed world. Issues particularly apparent in PNG include food insecurity[ 16 ], poor road systems, long distances between villages and ART prescribing sites, delays in on-time pill pick up as a result of road blocks, tribal fighting or lack of bus fare [ 17 ], widespread use of traditional medicinal plants [ 18 ] and drug stock-out. Furthermore, a variety of Christian denominations exists in PNG with different beliefs on HIV infection and ART, which may represent additional barriers to adherence.…”

Traditional Preparations and Methanol Extracts of Medicinal Plants from Papua New Guinea Exhibit Similar Cytochrome P450 Inhibition

“…Succus was prepared in the field from 17 species of medicinal plants that were previously analysed for inhibition of CYPs [ 9 ]. Some of the plants were collected in more than one location.…”

“…Inhibition assays were performed as previously described [ 9 ]. In brief, plant extracts were added to human liver microsomes enriched in their respective CYP subtype (Celsis).…”

“…Drugs interact with CYPs through two major mechanisms: enzyme inhibition and enhanced enzyme expression, termed induction [ 6 ]. In an effort to determine potential impact of traditional medicines on HIV/TB treatment efficacy, we previously assessed methanol extracts from 69 of the 100 most commonly used medicinal plants (as listed in UPNG Traditional Medicines Database [ 7 , 8 ]), collected from 7 PNG provinces, for human CYP induction and inhibition in vitro [ 9 ]. Close to two-thirds of the medicinal plant extracts exhibited potent CYP inhibition, while almost one-third of them significantly induced CYP expression.…”

Advance in studies on traditional Chinese medicines to treat infection with the hepatitis B virus and hepatitis C virus

“…Although the active compounds in TCMs have not been fully isolated and identified, a few have been found to be potential antivirals (14). Bioactive compounds extracted from natural products have characteristics similar to chemically synthesized medications and they can be easily assimilated and metabolized by the human body (15). Moreover, TCMs can be obtained from various organisms without the need for laborious or industrial chemosynthesis.…”