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Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria

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Abstract

Background and Objective

The use of herbal medicines is common in Africa, and patients often use a combination of herbs and drugs. Concurrent herbal and pharmaceuticals treatments can cause adverse effects through herb-drug interactions (HDI). This study evaluated the potential risk of HDI for five medicinal plants, Vernonia amygdalina, Ocimum gratissimum, Moringa oleifera, Azadirachta indica, and Picralima nitida, using in vitro assays. Patients with diabetes and some other disease conditions commonly use these medicinal plants in Nigeria, and little is known regarding their potential for drug interaction, despite their enormous use.

Methods

Crude extracts of the medicinal plants were evaluated for reversible and time-dependent inhibition (TDI) activity of six cytochrome P450 (CYP) enzymes using pooled human liver microsomes and cocktail probe-based assays. Enzyme activity was determined by quantifying marker metabolites' formation using liquid chromatography-mass spectrometry/mass spectrometry. The drug interaction potential was predicted for each herbal extract using the in vitro half-maximal inhibitory concentration (IC50) values and the percentage yield.

Results

O. gratissimum methanol extracts reversibly inhibited CYP 1A2, 2C8, 2C9 and 2C19 enzymes (IC50: 6.21 µg/ml, 2.96 µg/ml, 3.33 µg/ml and 1.37 µg/ml, respectively). Additionally, V. amygdalina methanol extract inhibited CYP2C8 activity (IC50: 5.71 µg/ml); P. nitida methanol and aqueous extracts inhibited CYP2D6 activity (IC50: 1.99 µg/ml and 2.36 µg/ml, respectively) while A. indica methanol extract inhibited CYP 3A4/5, 2C8 and 2C9 activity (IC50: 7.31 µg/ml, 9.97 µg/ml and 9.20 µg/ml, respectively). The extracts showed a potential for TDI of the enzymes when incubated at 200 µg/ml; V. amygdalina and A. indica methanol extracts exhibited TDI potential for all the major CYPs.

Conclusions

The medicinal plants inhibited CYP activity in vitro, with the potential to cause in vivo HDI. Clinical risk assessment and proactive monitoring are recommended for patients who use these medicinal plants concurrently with drugs that are cleared through CYP metabolism.

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Acknowledgements

The authors wish to thank Pfizer Inc. Pharmacokinetics, Dynamics and Metabolism Research Unit, Groton, CT, USA, for their help with the enzyme inhibition assay and generous donation of resources and Hang Ma for his assistance with the extraction of the medicinal plants.

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Authors and Affiliations

  1. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Rd, Kingston, RI, 02881, USA

    Ogochukwu Amaeze & Angela Slitt

  2. Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Groton, CT, USA

    Heather Eng, Lauren Horlbogen & Manthena V. S. Varma

  3. Department of Clinical Pharmacy and Biopharmacy, Faculty of Pharmacy, University of Lagos, Lagos, Nigeria

    Ogochukwu Amaeze

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  1. Ogochukwu Amaeze
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  2. Heather Eng
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  5. Angela Slitt
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Correspondence to Angela Slitt.

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Funding

This study was supported by funding made available through the Fulbright Foreign Students Scholarship to Ogochukwu Amaeze and the National Institute of Health (Grant Number P42ES027706). The funders had no role in the study design, data collection, analysis, decision to publish or manuscript preparation.

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All the authors declare that they have no conflict of interest.

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Availability of data and material

The datasets generated during and analyzed during the current study are freely available from the corresponding author on reasonable request.

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Author contributions

All authors contributed to the study conception and design. Ogochukwu Amaeze performed the extraction of the medicinal plants. Heather Eng and Lauren Horlbogen performed the enzyme inhibition experiments. Data analysis was carried out by Ogochukwu Amaeze, Heather Eng, Lauren Horlbogen and Angela Slitt. Ogochukwu Amaeze wrote the first draft of the manuscript; all authors edited and commented on previous versions of the manuscript. Manthena Varma and Angela Slitt performed critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Amaeze, O., Eng, H., Horlbogen, L. et al. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet 46, 437–450 (2021). https://doi.org/10.1007/s13318-021-00685-1

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