The modulation of carbonyl reductase 1 by polyphenols
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- Keywords
- Flavonoids, curcuminoids, induction, inhibition, polymorphism, stilbenes,
- MeSH
- Alcohol Oxidoreductases antagonists & inhibitors biosynthesis genetics metabolism MeSH
- Bupropion metabolism MeSH
- Butanones metabolism MeSH
- Butyrophenones metabolism MeSH
- Quinolizines metabolism MeSH
- Daunorubicin metabolism MeSH
- Doxorubicin metabolism MeSH
- Phenylpropionates metabolism MeSH
- Haloperidol metabolism MeSH
- Indoles metabolism MeSH
- Humans MeSH
- Nabumetone MeSH
- Neoplasms enzymology MeSH
- Polyphenols pharmacology MeSH
- Gene Expression Regulation, Enzymologic MeSH
- Substrate Specificity MeSH
- Xenobiotics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Alcohol Oxidoreductases MeSH
- Bupropion MeSH
- Butanones MeSH
- Butyrophenones MeSH
- CBR1 protein, human MeSH Browser
- Quinolizines MeSH
- Daunorubicin MeSH
- dolasetron MeSH Browser
- Doxorubicin MeSH
- Phenylpropionates MeSH
- Haloperidol MeSH
- Indoles MeSH
- loxoprofen MeSH Browser
- Nabumetone MeSH
- Polyphenols MeSH
- timiperone MeSH Browser
- Xenobiotics MeSH
Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain dehydrogenases/reductases family, has been detected in all human tissues. CBR1 catalyzes the reduction of many xenobiotics, including important drugs (e.g. anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and quinones. Moreover, it participates in the metabolism of a number of endogenous compounds and it may play a role in certain pathologies. Plant polyphenols are not only present in many human food sources, but are also a component of many popular dietary supplements and herbal medicines. Many studies reviewed herein have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids in the inhibition of the activity of CBR1. Interactions of these polyphenols with transcriptional factors, which regulate CBR1 expression, have also been reported in several studies. As CBR1 plays an important role in drug metabolism as well as in the protection of the organism against potentially harmful carbonyls, the modulation of its expression/activity may have significant pharmacological and/or toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but it may cause the worse detoxification of reactive carbonyls. Nevertheless, all known information about the interactions of polyphenols with CBR1 have only been based on the results of in vitro studies. With respect to the high importance of CBR1 and the frequent consumption of polyphenols, in vivo studies would be very helpful for the evaluation of risks/benefits of polyphenol interactions with CBR1.
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