In Vitro Reversible and Time-Dependent CYP450 Inhibition Profiles of Medicinal Herbal Plant Extracts Newbouldia laevis and Cassia abbreviata: Implications for Herb-Drug Interactions.

Ambroise Wonkam,Nicholas Thomford,Dee Blackhurst,Denis Chopera,Kevin Dzobo,Alfred Maroyi,Collet Dandara

doi:10.3390/molecules21070891

Abstract

This study evaluated the effects of Newbouldia laevis and Cassia abbreviata extracts on CYP450 enzyme activity. Recombinant CYP450 enzyme and fluorogenic substrates were used for evaluating inhibition, allowing the assessment of herb–drug interactions (HDI). Phytochemical fingerprinting was performed using UPLC-MS. The herbal extracts were risk ranked for HDI based on the IC50 values determined for each CYP enzyme. Newbouldia laevis inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities with Ki of 2.84 µg/mL, 1.55 µg/mL, and 1.23 µg/mL, respectively. N. laevis exhibited a TDI (4.17) effect on CYP1A2 but not CYP2C9 and CYP2C19 enzyme activities. Cassia abbreviata inhibited CYP1A2, CYP2C9, and CYP2C19 enzyme activities showing a Ki of 4.86 µg/mL, 5.98 µg/mL, and 1.58 µg/mL, respectively. TDI potency assessment for Cassia abbreviata showed it as a potential TDI candidate (1.64) for CYP1A2 and CYP2C19 (1.72). UPLC-MS analysis showed that Newbouldia laevis and Cassia abbreviata possess polyphenols that likely give them their therapeutic properties; some of them are likely to be responsible for the observed inhibition. The observations made in this study suggest the potential for these herbal compounds to interact, especially when co-administered with other medications metabolized by these CYP450 enzymes.

Highlights

African populations have used herbal medicines for many centuries
Given the varied amounts of compounds found in medicinal herbal plants, standardization parameters and development of marker profiles of commonly used medicinal plants are very important for maintaining the quality of herbal remedies and provide knowledge on the optimal concentrations of the various bio-constituents [25,26]
The aim of this study was to evaluate the cytochrome P450 (CYP450) inhibition activities of Newbouldia laevis and Cassia abbreviata extracts commonly used in West and Southern Africa for the treatment and/or management of common communicable and non-communicable diseases

Summary

Introduction

African populations have used herbal medicines for many centuries. Knowledge regarding specific plants and parts of these plants and their function in disease treatment is traditionally passedMolecules 2016, 21, 891; doi:10.3390/molecules21070891 www.mdpi.com/journal/moleculesMolecules 2016, 21, 891 on from one generation to the next. With the boom in conventional therapeutic drugs, the utilization of herbal remedies sometimes in combination with other medications has increased tremendously over the last decade [1,2]. It has been demonstrated over the years that herbal remedies possess great therapeutic potential in managing and treating a number of diseases including malaria, hypertension, HIV/AIDS, and cancer. Evidence available shows that there are potential interactions between drugs and herbs, some with fatal clinical outcomes [5,6,7]. Despite these fatal herb-drug clinical outcomes, there is still limited information on monitoring herb–drug interactions [8]

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Discussion

Conclusion