Effects of Eleutheroside B and Eleutheroside E on activity of cytochrome P450 in rat liver microsomes

Sixun Guo,Sheng Tai,Yan Liu,Gaofeng Liu,Zhiping Lin,Shuo Yin

doi:10.1186/1472-6882-14-1

Abstract

BackgroundChemicals of herbal products may cause unexpected toxicity or adverse effect by the potential for alteration of the activity of CYP450 when co-administered with other drugs. Eleutherococcus senticosus (ES), has been widely used as a traditional herbal medicine and popular herbal dietary supplements, and often co-administered with many other drugs. The main bioactive constituents of ES were considered to be eleutherosides including eleutheroside B (EB) and eleutheroside E (EE). This study was to investigate the effects of EB and EE on CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in rat liver microsomes in vitro.MethodProbe drugs of tolbutamide (TB), dextromethorphan (DM), chlorzoxazone (CLZ) and testosterone (TS) as well as eleutherosides of different concentrations were added to incubation systems of rat liver microsomes in vitro. After incubation, validated HPLC methods were used to quantify relevant metabolites.ResultsThe results suggested that EB and EE exhibited weak inhibition against the activity of CYP2C9 and CYP2E1, but no effects on CYP2D6 and CYP3A4 activity. The IC50 values for EB and EE were calculated to be 193.20 μM and 188.36 μM for CYP2E1, 595.66 μM and 261.82 μM for CYP2C9, respectively. Kinetic analysis showed that inhibitions of CYP2E1 by EB and EE were best fit to mixed-type with Ki value of 183.95 μM and 171.63 μM, respectively.ConclusionsThese results indicate that EB and EE may inhibit the metabolism of drugs metabolized via CYP2C9 and CYP2E1, and have the potential to increase the toxicity of the drugs.

Highlights

Chemicals of herbal products may cause unexpected toxicity or adverse effect by the potential for alteration of the activity of Cytochrome P450 (CYP450) when co-administered with other drugs
The results suggested that eleutheroside B (EB) and eleutheroside E (EE) exhibited weak inhibition against the activity of CYP2C9 and CYP2E1, but no effects on CYP2D6 and CYP3A4 activity
Kinetic analysis showed that inhibitions of CYP2E1 by EB and EE were best fit to mixed-type with Ki value of 183.95 μM and 171.63 μM, respectively

Summary

Introduction

Chemicals of herbal products may cause unexpected toxicity or adverse effect by the potential for alteration of the activity of CYP450 when co-administered with other drugs. It is a medicinal herb that dates back more than 2000 years according to Chinese medicine records and is known as a powerful tonic herb with an impressive range of health benefits This medicinal plant is popular in China and Russia, and one of the 10 popular herbal dietary supplements used in the United States [1]. CYP3A4, CYP2D6, CYP2C9 and CYP2E1 have been estimated to be involved in the metabolism of approximately 85% of the drugs in clinical practice [18]. Since these subtypes metabolize numerous drugs, drug-drug interactions (DDIs) can potentially occur when multiple drugs are co-administered. Inhibition of CYP450 enzymes is the most important reason caused DDIs, which raises the toxicity of drugs

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Conclusion