Time-dependent Inhibition of CYP2C8 and CYP2C19 by Hedera helix Extracts, A Traditional Respiratory Herbal Medicine.

Shaheed Rehman,Min Choi,In Kim,Yonghui Zhang,Seung Kim,Hye Yoo

doi:10.3390/molecules22071241

Abstract

The extract of Hedera helix L. (Araliaceae), a well-known folk medicine, has been popularly used to treat respiratory problems, worldwide. It is very likely that this herbal extract is taken in combination with conventional drugs. The present study aimed to evaluate the effects of H. helix extract on cytochrome P450 (CYP) enzyme-mediated metabolism to predict the potential for herb–drug interactions. A cocktail probe assay was used to measure the inhibitory effect of CYP. H. helix extracts were incubated with pooled human liver microsomes or CYP isozymes with CYP-specific substrates, and the formation of specific metabolites was investigated to measure the inhibitory effects. H. helix showed significant inhibitory effects on CYP2C8, CYP2C19 and CYP2D6 in a concentration-dependent manner. In recombinant CYP2C8, CYP2C19 and CYP2D6 isozymes, the IC50 values of the extract were 0.08 ± 0.01, 0.58 ± 0.03 and 6.72 ± 0.22 mg/mL, respectively. Further investigation showed that H. helix extract has a positive time-dependent inhibition property on both CYP2C8 and CYP2C19 with IC50 shift value of 2.77 ± 0.12 and 6.31 ± 0.25, respectively. Based on this in vitro investigation, consumption of herbal medicines or dietary supplements containing H. helix extracts requires careful attention to avoid any CYP-based interactions.

Highlights

Hedera helix L. (Araliaceae), known as common ivy or English ivy, has been traditionally used for the treatment of respiratory disorders [1]
cytochrome P450 (CYP) Inhibition Assay in Pooled Human Liver Microsomes
We investigated the inhibitory effect of H. helix extract on CYP enzymes in pooled human liver microsomes

Summary

Introduction

Hedera helix L. (Araliaceae), known as common ivy or English ivy, has been traditionally used for the treatment of respiratory disorders [1]. (Araliaceae), known as common ivy or English ivy, has been traditionally used for the treatment of respiratory disorders [1]. The pharmacological data of H. helix extracts, including its bronchodilator, antibacterial, bronchospasmolytic, and expectorant effects, have supported its traditional use as a natural remedy for respiratory illness [2,3]. It is one of the top-selling herbal respiratory medicines in many countries worldwide, and it is popularly used for the treatment of cough and cough-related problems [4,5]. C, α-hederin, aglycone hederagenin, kaempferol and quercetin of H. helix extract [6]. Kaempferol and quercetin significantly reduced the contraction of guinea-pig isolated ileum induced by prostaglandin E2 and leukotriene D4 [7]. The saponin from H. helix inhibited the terbutaline-stimulated internalization of the β2-adrenergic receptor in alveolar epithelial type-II cell line to explain its Molecules 2017, 22, 1241; doi:10.3390/molecules22071241 www.mdpi.com/journal/molecules

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Conclusion