Inhibition of Major Drug Metabolizing CYPs by Common Herbal Medicines used by HIV/AIDS Patients in Africa– Implications for Herb- Drug Interactions
Charles Awortwe, Patrick J. Bouic, Collen M. Masimirembwa and Bernd Rosenkranz
Affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Stellenbosch, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
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
Keywords: Cytochrome P450s, fluorometric assay, herb-drug interactions, parallel artificial membrane permeability assays.
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