Inhibition of Major Drug Metabolizing CYPs by Common Herbal Medicines used by HIV/AIDS Patients in Africa– Implications for Herb- Drug Interactions

Abstract

The purpose of this study was to evaluate the potential risk of common herbal medicines used by HIV-infected patients in Africa for herb-drug interactions (HDI). High throughput screening assays consisting of recombinant Cytochrome P450 enzymes (CYPs) and fluorescent probes, and parallel artificial membrane permeability assays (PAMPA) were used. The potential of herbal medicines to cause HDI was ranked according to FDA guidelines for reversible inhibition and categorization of time dependent inhibition was based on the normalized ratio. CYPs 1A2 and 3A4 were most inhibited by the herbal extracts. H. hemerocallidea (IC50 = 0.63 μg/mL and 58 μg/mL) and E. purpurea (IC50 = 20 μg/mL and 12 μg/mL) were the potent inhibitors of CYPs 1A2 and 3A4 respectively. L. frutescens and H. hemerocallidea showed clear time dependent inhibition on CYP3A4. Furthermore, the inhibitory effect of both H. hemerocallidea and L. frutescens before and after PAMPA were identical. The results indicate potential HDI of H. hemerocallidea, L. frutescens and E. purpurea with substrates of the affected enzymes if maximum in vivo concentration is achieved.

Concurrent use of traditional medicine and ART: Perspectives of patients, providers and traditional healers in Durban, South Africa

“…In considering the clinical possibility of a dual approach to HIV treatment and care, safety during concurrent ART and TAM practices, rather than changes in ART adherence patterns, becomes the primary issue to address. There is already a growing body of pharmacological research concerning herb-drug interactions as well as the use of plants like Hypoxishemerocallidea and Sutherlandiafrutescens to treat HIV primarily by enhancing the immune system or some with actual antiviral properties (Awortwe, Bouic, Masimirembwa, & Rosenkranz, B., 2014; Chinsembu & Hedimbi, 2009; Mills, Cooper, Seely, & Kanfer, 2005; Rosenberg et al, 2013); findings here affirm the importance of continuing to advance this important area of study.…”

Concurrent use of Antiretroviral and African traditional medicines amongst people living with HIV/AIDS (PLWA) in the eThekwini Metropolitan area of KwaZulu Natal

“…Furthermore, a 2014 laboratory study validated the findings of Mills and showed that H. hypoxis, E. purpurea, M. oleifera,T. officinale and L. frutescens inhibited major drug metabolising enzymes and had the potential to interact with ARV 17 .…”

“…It could be surmised that even greater access to ARV through universal access programs since 2008 and the reduced costs of these treatments would have resulted in a reduced demand for ATM 6 . Furthermore, there was growing evidence of invitro studies which indicated that commonly used South African ATM interacted with ARV 15,16,17 . Reduced ATM use in the current study may also be attributed to efforts by health care professionals in communication the potential for herb-drug interactions (HDI) to patients during pre-counselling sessions.…”

Echinacea purpureaup-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway

“…In brief, 100 µL of cofactors mixture, control protein (0.05 mg of protein/mL) and G-6-PDH were added to each well. Initial readings were taken to record any autofluorescence, and the plates were incubated at 37 °C for 30 min after addition of 3 µM 7-ethoxy-3-cyanocoumarin (CYP1A2 substrates) or 10 µM 7-benzyloxy-4-trifluoromethylcoumarin (CYP3A4 substrate) (100 mL) to respective wells (Awortwe et al, 2014; Renwick et al, 2000). The reaction was terminated by the addition of 50 µL of ice-cold acetonitrile/0.5 M Tris base (80:20).…”