Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation
Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR)....
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doaj-de2fc41d249e46478885d4594166a1932020-11-25T02:03:42ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882012-01-01201210.1155/2012/242810242810Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor ActivationYun-Ping Lim0Chia-Yun Ma1Cheng-Ling Liu2Yu-Hsien Lin3Miao-Lin Hu4Jih-Jung Chen5Dong-Zong Hung6Wen-Tsong Hsieh7Jin-Ding Huang8Department of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, TaiwanDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, TaiwanDepartment of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, TaiwanDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, TaiwanDepartment of Food Science and Biotechnology, National Chung Hsing University, Taichung 40227, TaiwanGraduate Institute of Pharmaceutical Technology, Tajen University, Pingtung 90741, TaiwanDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, TaiwanSchool of Medicine and Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, TaiwanInstitute of Biopharmaceutical Sciences, Medical College, National Cheng Kung University, Tainan 70101, TaiwanInconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.http://dx.doi.org/10.1155/2012/242810 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yun-Ping Lim Chia-Yun Ma Cheng-Ling Liu Yu-Hsien Lin Miao-Lin Hu Jih-Jung Chen Dong-Zong Hung Wen-Tsong Hsieh Jin-Ding Huang |
spellingShingle |
Yun-Ping Lim Chia-Yun Ma Cheng-Ling Liu Yu-Hsien Lin Miao-Lin Hu Jih-Jung Chen Dong-Zong Hung Wen-Tsong Hsieh Jin-Ding Huang Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation Evidence-Based Complementary and Alternative Medicine |
author_facet |
Yun-Ping Lim Chia-Yun Ma Cheng-Ling Liu Yu-Hsien Lin Miao-Lin Hu Jih-Jung Chen Dong-Zong Hung Wen-Tsong Hsieh Jin-Ding Huang |
author_sort |
Yun-Ping Lim |
title |
Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation |
title_short |
Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation |
title_full |
Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation |
title_fullStr |
Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation |
title_full_unstemmed |
Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation |
title_sort |
sesamin: a naturally occurring lignan inhibits cyp3a4 by antagonizing the pregnane x receptor activation |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2012-01-01 |
description |
Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety. |
url |
http://dx.doi.org/10.1155/2012/242810 |
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