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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

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

Supporting Information



Publication History

Received: 18 October 2022

Accepted after revision: 23 May 2023

Accepted Manuscript online:
26 May 2023

Article published online:
14 July 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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