P450 cytochrome resveratrol

Resveratrol may be beneficial particularly in postmenopausal women for cardioprotection and osteoporosis prevention. " This effect may be due to the estrogenic effect of resveratrol. Moreover, as shown above (Section 26.6.7) by its ability to modulate activity of cytochrome P450 enzymes, resveratrol would have positive effect as a chemopreventive agent. However, no studies have yet been conducted to examine the possible clinical application of resveratrol for cardioprotection, osteoporosis prevention, or chemoprevention. 

Owing to the fact that ethyl ethers are especially effective substrates for CYP1A1 [184], the probe possesses an ethyl group on the phenolic oxygen of the trimethyl lock. In vitro, fluorescence was manifested by CYP1A1 isozyme with Kcat/KM 8.8 x 103 M-1s 1 and KM 0.09 pM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), and its repression by the chemoprotectant resveratrol. 

Yu, C., Shin, Y.G., Kosmeder, J.W., Pezzuto, J.M., and van Breemen, R.B., Liquid chromatog-raphy/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun. Mass Spectrom., 17, 307, 2003. 

Naturally occurring phyllodulcin was orally administered to rats to investigate its metabolism using three-dimensional HPLC to analyze the urinary metabolites [97]. Potter et al. demonstrated that resveratrol (1) could be converted to piceatannol by the action of cytochrome P450 enzyme CYPIBI in vivo [379]. The fate of kobophenol A in rats has been studied and the major metabolites, koboquinone A (745), koboquinone B (746) and koboquinone C (767), have been characterized [338]. 

Potter, G.A., L.H. Patterson, E. Wanogho, P.J. Perry, P.C. Butler, T. Ijaz et al. (2002). The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYPIBI. Br. J. Cancer 86, 774-778. 

Chan WK, Delucchi AB. Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci 2000 67 3103-3112. 

Chang TK, Lee WB, Ko HH (2000) trans-Resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 IBl. Can J Physiol Pharmacol 78 874-881 Chang WH, Chen CH, Gau RJ, Lin CC, Tsai CL, Tsai K, Lu FJ (2002) Effect of baicalein on apoptosis of the human Hep G2 cell line was induced by mitochondrial dysfunction. Planta Med 68 302-306 Chao SH, Price DH (2001)Flavopitidol inactivates P-TEFb and blocks most RNA polymerase 11 transcription in vivo. J Biol Chem 276 31793-31799... 

A study in animals found that pretreatment with oral ciclosporin had no effect on the pharmacokinetics of alcohol or acetaldehyde. This suggests that any difference in the alcohol consumption of patients taking ciclosporin is unlikely to have a pharmacokinetic basis. The mechanism by which red wine exerts its effect is not known. White wine does not appear to affect ciclosporin pharmacokinetics," so the interaction is not believed to be an effect of alcohol. Antioxidants in red wine such as resveratrol may inactivate the cytochrome P450 isoenzyme CYP3A4 and this would also be expected to increase ciclosporin levels. The solubility of ciclosporin is decreased in red wine and it is possible that substances in red wine bind ciclosporin in the gastrointestinal tract and reduce its bioavailability. Another study by the same authors suggested that ciclosporin absorption is possibly impaired by P-glycoprotein induction. ... 

Piver B, Berthou F, Dreano Y, Eucas D (2003) Differential inhibition of human cytochrome P450 enzymes by epsilon-viniferin, the dimer of resveratrol comparison with resveratrol and polyphenols from alcoholized beverages. Life Sci 73 1199-1213... 

Mikstacka, R, Przybylska, D., Rimando, A.M, and Baer-Dubowska, W. (2007) Inhibition of human recombinant cytochromes P450 CYPlAl and CYPIBI by trans-resveratrol methyl ethers. Mol Nutr. Food Res., 51, 517-524,... 

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