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Planta Med 2014; 80(06): 493-497
DOI: 10.1055/s-0034-1368302
Pharmacokinetic Investigations
Letters
Georg Thieme Verlag KG Stuttgart · New York

Metabolism of Chamaechromone In Vitro with Human Liver Microsomes and Recombinant Human Drug-Metabolizing Enzymes

Yan Lou
1   The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
2   Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
,
Haihong Hu
2   Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
,
Yunqing Qiu
1   The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
,
Jinqi Zheng
3   Zhejiang Institute for Food and Drug Control, Hangzhou, Peopleʼs Republic of China
,
Linrun Wang
1   The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
,
Xingguo Zhang
1   The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
,
Su Zeng
2   Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, Peopleʼs Republic of China
› Author Affiliations
Further Information

Publication History

received 28 November 2013
revised 16 February 2014

accepted 27 February 2014

Publication Date:
31 March 2014 (online)

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Abstract

Chamaechromone is a major component in the dried roots of Stellera chamaejasme with antihepatitis B virus and insecticidal activity. In this study, metabolic profiles of chamaechromone were investigated in human liver microsomes. One monohydroxide and two monoglucuronides of chamaechromone were identified. The enzyme kinetics for both hydroxylation and glucuronidation were fitted to the Michaelis–Menten equation. The hydroxylation of chamaechromone was inhibited by α-naphthoflavone, and predominantly catalyzed by recombinant human cytochrome P450 1A2, whereas the glucuronidation was inhibited by quercetin, 1-naphthol, and fluconazole, and mainly catalyzed by recombinant human UDP-glucuronosyltransferase 1A3, 1A7, 1A9, and 2B7.

Key words

Stellera chamaejasme - Thymelaeaceae - chamaechromone - metabolite - in vitro - human liver microsomes - recombinant human enzymes

Supporting Information

 

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