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Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling
Qiao, Xue; Ji, Shuai; Yu, Si-wang; Lin, Xiong-hao; Jin, Hong-wei; Duan, Yao-kai; Zhang, Liang-ren; Guo, De-an; Ye, Min
关键词Cyp450 Herb-drug Interaction Isoliquiritigenin Licorice Liquiritigenin
刊名AAPS JOURNAL
2014
DOI10.1208/s12248-013-9544-9
16期:1页:101-113
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]IN-VITRO ; MASS-SPECTROMETRY ; HERBAL MEDICINE ; INHIBITION ; 3A4 ; ACID ; 2C9 ; 2D6
英文摘要

Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes 1A2, 2C9, 2C19, 2D6, and 3A4 were then selected for examination of their structural features by molecular docking to determine their molecular interaction with several P450 isozymes. Based on the present in vitro inhibition findings, along with our previous in vivo metabolic studies and the prevalence of individual compounds in licorice extract, we identified several licorice constituents, viz., liquiritigenin, isoliquiritigenin, together with seven isoprenylated flavonoids and arylcoumarins, which could be key components responsible for the herb-drug interaction between cytochrome P450 and licorice. In addition, hydrophilic flavonoid glycosides and saponins may be converted into these P450 inhibitors in vivo. These studies represent a comprehensive examination of the potential effects of licorice components on the metabolic activities of P450 enzymes.

语种英语
WOS记录号WOS:000329165600012
引用统计
被引频次:23[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55747
专题北京大学药学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学药学院_化学生物学系
北京大学药学院_药物化学系
北京大学药学院_天然药物学系
作者单位Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Qiao, Xue,Ji, Shuai,Yu, Si-wang,et al. Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling[J]. AAPS JOURNAL,2014,16(1):101-113.
APA Qiao, Xue.,Ji, Shuai.,Yu, Si-wang.,Lin, Xiong-hao.,Jin, Hong-wei.,...&Ye, Min.(2014).Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling.AAPS JOURNAL,16(1),101-113.
MLA Qiao, Xue,et al."Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling".AAPS JOURNAL 16.1(2014):101-113.
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