In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism

Wenwen Zhang; Yice Zhang; Chengming Wen; Xuehua Jiang; Ling Wang

doi:10.1055/a-2102-0648

Planta Medica, Table of Contents

CC BY-NC-ND 4.0 · Planta Med 2023; 89(13): 1195-1203
DOI: 10.1055/a-2102-0648

Biological and Pharmacological Activity

Original Papers

In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism

Authors

Wenwen Zhang

¹Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China

²Deparment of Pharmacy, Xiʼan Childrenʼs Hospital, The Affiliated Children Hospital of Xiʼan Jiaotong University, Xiʼan, China
Yice Zhang

¹Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China
Chengming Wen

¹Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China
Xuehua Jiang

¹Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China
Ling Wang

¹Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China

Abstract

Silybin is a flavonol compound with a variety of physiological properties, such as hepatoprotective, anti-fibrogenic, and hypocholesterolemic effects. Although the in vivo and in vitro effects of silybin are frequently reported, studies on herb–drug interactions have yet to be performed. With the discovery of multiple important substrates of CYP2B6 recently, there is a growing body of evidence indicating that CYP2B6 plays a much larger role in human drug metabolism than previously thought.

The purpose of this study is to determine how silybin affects the CYP2B6 enzymeʼs activity, as well as to clarify the molecular mechanisms for inhibition by silybin. The results showed that silybin inhibited CYP2B6 activity in liver microsomes in a non-competitive manner, with IC₅₀ and K_i values of 13.9 µM and 38.4 µM, respectively. Further investigations revealed that silybin could down-regulate the expression of CYP2B6 protein in HepaRG cells. The hydrogen bond conformation of silybin in the active site of the CYP2B6 isoform was revealed by a molecular docking study. Collectively, our findings verify that silybin is an inhibitor of CYP2B6 and explain the molecular mechanism of inhibition. This can lead to a better understanding of the herb–drug interaction between silybin and the substrates of the CYP2B6 enzyme, as well as a more rational clinical use of silybin.

Key words

silybin - Silybum marianum - CYP2B6 - inhibition - Liver microsomes - Interaction

Full Text

References

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Supplementary Material

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