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1.
Toxicol Lett. 2001 Dec 15;125(1-3):83-91.

Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components.

Author information

1
Laboratory of Biochemistry, EA 948, Faculty of Medicine and I3S, 29285, cedex, Brest, France.

Abstract

Resveratrol (RESV), present at concentrations of about 10 microM in red wine, has been found to inhibit events associated with tumor initiation, promotion and progression. The mechanism involved could be the inhibition of activities catalyzed by cytochromes P450 (CYPs), which activate procarcinogens. This led us to investigate the inhibitory effect of RESV on CYP1A, CYP2E1 and CYP3A enzymatic activities and to compare it to that of non volatile compounds present in red wine. Red wine solids (RWS) were prepared by evaporating one volume of red wine to dryness followed by reconstitution with five volumes of buffer (20% natural strength). CYP activities were determined in microsomes from rat liver, human liver or cells containing cDNA-expressed CYPs. Testosterone, chlorzoxazone, and ethoxyresorufin were used as selective substrates for CYP3A, CYP2E1 and CYP1A1/1A2, respectively. RESV and RWS were found to be irreversible (probably mechanism-based) inhibitors for CYP3A4 and non competitive reversible inhibitors for CYP2E1. Their inhibitory potency was assessed using IC(50) values that were found within 4-150 microM for RESV and 0.3-9% natural strength for RWS. Non volatile compounds of other beverages such as white wine, grape juice or Xtra Old Cognac(R) displayed lower inhibitory effect on CYP activities than RWS. When considering the concentration of RESV in red wine (2 microM for 20% natural strength), it appears that RSW inhibitory effect was not only due to RESV, but also to other compounds whose identification would prove to be worthwhile because of their possible chemopreventive properties.

PMID:
11701226
[Indexed for MEDLINE]
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2.
Life Sci. 2003 Jul 18;73(9):1199-213.

Differential inhibition of human cytochrome P450 enzymes by epsilon-viniferin, the dimer of resveratrol: comparison with resveratrol and polyphenols from alcoholized beverages.

Author information

1
Laboratory of Biochemistry, EA 948, Faculty of Medicine and I3S, 29285 Brest Cedex, France.

Abstract

epsilon-Viniferin, a dimer of resveratrol, was isolated in wine at concentration between 0.5 and 5 microM. As resveratrol and polyphenols from red wine were reported to inhibit cytochrome P450 (CYP) activities, this led us to investigate the inhibitory effects of epsilon-viniferin on human CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2E1, CYP3A4 and CYP4A activities. These effects were compared to those of resveratrol and non volatiles compounds from red wine or various Cognac(R) beverages (enriched with oak-polyphenols). Assays were carried out on human liver microsomes and heterologously expressed CYPs. Ethoxyresorufin, coumarin, benzoxyresorufin, chlorzoxazone, testosterone and lauric acid were used as selective substrates for CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2E1, CYP3A4 and CYP4A, respectively. epsilon-viniferin displayed a more potent inhibitory effect than resveratrol for all the CYP activities tested (Ki 0.5 to 20 microM vs. 10 to 100 microM, respectively). This effect was not due to an inhibition of the NADPH reductase. A particularly potent inhibitory effect was shown for CYP1A1, CYP1B1 and CYP2B6 which are involved in bioactivation of numerous carcinogens. epsilon-viniferin was not a mechanism-based inhibitor of human CYPs. It displayed, like resveratrol, mixed-type inhibitions for all the CYP tested, except for CYP2E1 (non-competitive). Comparison of the inhibitory effects exerted on CYP activities by epsilon-viniferin, resveratrol and non volatile components from red wine or various Cognac beverages showed that neither resveratrol, nor epsilon-viniferin is the main CYP inhibitor present in red wine solids.

PMID:
12818727
DOI:
10.1016/s0024-3205(03)00420-x
[Indexed for MEDLINE]
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