Interactions of herbs with cytochrome P450

Zhou, S, Gao, Y, Huang, M, Xu, A and Paxton, J 2003, 'Interactions of herbs with cytochrome P450', Drug Metabolism Reviews, vol. 35, no. 1, pp. 35-98.

Document type: Journal Article
Collection: Journal Articles

Title Interactions of herbs with cytochrome P450
Author(s) Zhou, S
Gao, Y
Huang, M
Xu, A
Paxton, J
Year 2003
Journal name Drug Metabolism Reviews
Volume number 35
Issue number 1
Start page 35
End page 98
Total pages 64
Publisher Informa Healthcare
Abstract A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb–drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products is complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb–drug metabolic interactions is difficult. However, herb–CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb–CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb–CYP interactions. Read More:
Keyword(s) 1 nitrosopiperidine
8 tetrachlorodibenzo para dioxin
allyl sulfide
cytochrome P450
cytochrome P450 1A2
cytochrome P450 2C19
cytochrome P450 2C9
cytochrome P450 2D6
cytochrome P450 3A4
garlic extract
ginseng extract
Glycyrrhiza extract
herbaceous agent
Hypericum perforatum extract
natural product
organosulfur derivative
pregnane X receptor
reduced nicotinamide adenine dinucleotide phosphate
retinoic acid
sulfone derivative
unindexed drug
DOI - identifier 10.1081/DMR-120018248
ISSN 0360-2532
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