Planta Med 2014; 80(13): 1097-1106
DOI: 10.1055/s-0034-1383000
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Cytochrome P450 2C9 Expression and Activity In Vitro by Allyl Isothiocyanate

Yun-Ping Lim
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
2   Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan, ROC
,
Wei-Cheng Chen
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
3   Department of Pharmacy, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, Taiwan, ROC
,
Ching-Hao Cheng
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
4   Department of Pharmacy, Changhua Show Chwan Memorial Hospital, Changhua, Taiwan, ROC
,
Wei-Chih Ma
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
,
Yu-Hsien Lin
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
,
Cing-Yu Chen
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
,
Dong-Zong Hung
1   Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC
2   Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan, ROC
,
Jih-Jung Chen
5   Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, Taiwan, ROC
,
Tsuyoshi Yokoi
6   Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan
,
Miki Nakajima
6   Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan
,
Chao-Jung Chen
7   Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan, ROC
8   Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, ROC
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 27. März 2014
revised 06. Juni 2014

accepted 21. Juli 2014

Publikationsdatum:
08. September 2014 (online)

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Abstract

The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported. In this study, we found that allyl isothiocyanate reduced catalytic activity, messenger ribonucleic acid, and protein expression of cytochrome P450 2C9 in HepaRG cells. An investigation of the transcriptional activity of the pregnane X receptor and the constitutive androstane receptor revealed that allyl isothiocyanate disrupted the transcriptional coregulation effects of the pregnane X receptor/constitutive androstane receptor with several important coregulators and interfered with the assembly of transcriptional complexes of the cytochrome P450 2C9 pregnane X receptor/constitutive androstane receptor-response element. The decrease of cytochrome P450 2C9 expression and activity mediated by allyl isothiocyanate suggested that this agent could alter the metabolism of drugs metabolized by cytochrome P450 2C9. This may cause food/dietary supplement-drug interactions or alter the therapeutic effects, and even the toxicity of drugs coadministered with allyl isothiocyanate. Since the consumption of allyl isothiocyanate-containing food/dietary supplements continues to increase, it is important to predict and ultimately avoid interactions with concomitant drugs. It is required that these possible pharmacokinetic interactions be characterized and the recommendations available to patients and healthcare professionals be improved.