Red wine and components flavonoids inhibit UGT2B17 in vitro

Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analysed using HPLC and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8% the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HLPC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 M despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolising enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the healt

Formation and degradation of furfuryl alcohol, 5-methylfurfuryl alcohol, vanillyl alcohol, and their ethyl ehters in barrel-aged wines.

Furfural, 5-methylfurfural, and vanillin co-occurred in 64 barrel-aged red, white, and model wines with the reduction products, furfuryl alcohol, 5-methylfurfuryl alcohol, and vanillyl alcohol, and with the corresponding ethyl ethers of these alcohols. Hydrolytic studies in a model wine have shown that 5-methylfurfuryl ethyl ether is formed rapidly from 5-methylfurfuryl alcohol, but both decomposed quickly under the conditions. Vanillyl ethyl ether was also formed relatively rapidly, and both this ether and vanillyl alcohol were stable in the model wine. The formation of furfuryl ethyl ether from furfuryl alcohol and the subsequent decomposition of these two compounds were comparatively slow. The relative concentration of these aromatic alcohols and ethers in the barrel-aged wines was consistent with the observed stability of the furan derivatives, but low concentrations of vanillyl alcohol and vanillyl ethyl ether observed in all samples showed that factors other than solvolytic degradation were responsible for reducing the concentration of these compounds in wine. Furfuryl ethyl ether, which had an aroma threshold of 430 µg/L in a white wine, was found at approximate concentrations of up to 230 µg/L in the wines.Spillman, Philip J. ; Pollnitz, Alan P. ; Liacopoulos, Dimitra ; Pardon, Kevin H. ; Sefton, Mark A

The location of 2,4,6-trichloroanisole in a batch of contaminated wine corks

Straight wine corks, from a batch with a high proportion of contamination with 2,4,6-trichloroanisole (TCA), were dissected into various sections and the TCA content of these fractions was determined. TCA was found to be concentrated in the outside portion of the cork, and also in the older bark. There was no significant difference in TCA content between the lenticel and non-lenticel cork fractions, between the light and dark portions of the growth rings, nor between the ends and centre parts of the corks. The concentration of TCA in the outer part of the corks indicates that the biomethylation step in the formation of TCA in these corks followed the punching stage of production

Accumulation of vanillin during barrel-aging of white, red, and model wines.

A method for the rapid and accurate analysis of vanillin in wine, using stable isotope dilution analysis and gas chromatography/mass spectrometry, has been developed and applied to 64 oak barrel-aged white, red, and model wines. Following barrel fermentation and maturation on yeast lees, the concentration of vanillin in the white wines was only about one-third of that in the model wines stored for the same period. Once the yeast lees were removed, however, the white and model wines accumulated vanillin at a similar rate, which indicated that biological reduction of vanillin occurred only prior to racking. After 93 weeks in barrels, the concentration of vanillin in the red wines was less than one-half that in the model wines, and vanillin was further depleted during subsequent bottle storage of the red wines for 2 years at cellar temperature. For the model and red wines, the mean concentration of vanillin in barrels made from French oak, seasoned and coopered in Australia, was significantly higher than that for wines stored in barrels made from the same wood, but seasoned and coopered in France. In the white wines, extensive biological transformation of vanillin associated with yeast activity during the initial weeks of maturation appears to have nullified this seasoning/ coopering effect. Oak origin had no significant influence on the final vanillin concentration in the wines.Philip J. Spillman, Alan P. Pollnitz, Dimitra Liacopoulos, George K. Skouroumounis, and Mark A. Sefto

Quantitative analysis of geraniol, nerol, linalool, and a-terpineol in wine

A mixture of [²H₇]-geraniol, [²H₇]-nerol, [²H₇]-linalool and [²H₇]-f-terpineol was prepared for use as internal standards in a rapid and accurate analytical method, employing gas chromatography-mass spectrometry (GC/MS), to determine the concentration of geraniol, nerol, linalool and f-terpineol in wine. The method avoids the possible formation, degradation and interconversion of these compounds during their analysis