Role of phase 2 drug-metabolizing enzymes modulated by extracts from 78 herbal medicines in detoxification of electrophiles and lung cancer chemotherapy
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- Ohnuma Tomokazu
- Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Matsumoto Takashi
- Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Komatsu Takao
- Nippon Chemiphar Co. Ltd.
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- Nishiyama Takahito
- Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Ogura Kenichiro
- Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- Iwata Hiroshi
- Mitsubishi Chemical Medience Corp.
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- Hiratsuka Akira
- Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Abstract
Phase 2 drug-metabolizing enzymes (DMEs), such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), play a major role in the cellular detoxification of pharmaceutical agents and carcinogens. Previously, we reported the inhibitory effects of human liver microsomal cytochrome P450 3A4 and 2D6, phase 1 DMEs, by extracts from 78 herbal medicines. In the present study, we investigated whether phase 2 DME activity in mammalian cells was affected by the herbal extracts. Among the herbal extracts tested, GST and NQO1 activities in Clone 9 cells, a cultured cell line from normal rat liver, were increased more than 1.5-fold by treatment with Incised Notopterygium Rhizome, Magnolia Bark, Saussurea Root, and Magnolia Flower extracts. On the other hand, both of those activities were decreased to less than one-fifth by treatment with Cassia Bark and Rhubarb extracts. Pretreatment of Clone 9 cells with the former four extracts that induced phase 2 DMEs resulted in protection against the cytotoxicities of the electrophiles menadione and 1-chloro-2,4-dinitrobenzene. In contrast, GST and NQO1 activities in human lung cancer A549 cells, which are known to have a high metabolism and show resistance to anticancer drugs, was significantly decreased by treatment with the Cassia Bark extract. These results suggest that phase 2 DME activity may be modulated by herbal medicines, and the modulation of phase 2 DMEs by herbal medicines might affect the action of concomitant drugs and the detoxification of carcinogens.
Journal
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- Journal of Traditional Medicines
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Journal of Traditional Medicines 27 (3), 122-133, 2010
Medical and Pharmaceutical Society for WAKAN-YAKU
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Details 詳細情報について
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- CRID
- 1390001205233242240
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- NII Article ID
- 130004942364
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- NII Book ID
- AA12035198
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- ISSN
- 18813747
- 18801447
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- NDL BIB ID
- 10763056
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- CiNii Articles
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- Abstract License Flag
- Disallowed