Apart from chlorogenic and p coumaric acids glucuronidation activity was selleck chemicals reduced by each of the compounds in vary ing degrees. The inhibitory action of 4 ethylphenol is also displayed in Table 1. The results show the reduction in testosterone glucuronidation at initial testosterone concentrations of 100 uM, 50 uM and 20 uM. Quercetin was selected from the initial high concentra tion screening assay for further study as it exhibited the highest level of inhibition at 72%. Reducing the testosterone levels to 20 uM resulted in inhibition of 34 18% by a low concentration of quercetin, in a concentration dependent manner, despite the 10 fold excess in testosterone levels. In addition, for a quercetin concentration of 2 uM, increasing testosterone levels to 30 uM resulted in a reduction in inhibition from 18% to 2% suggesting that the mechanism is by competitive inhibition.

Discussion This report extends the previous study which demon strated that tea and its component flavones competi tively inhibit testosterone glucuronidation by UGT2B17. The results of this study showed that phenolic compounds commonly found in red wine, but also in many other foods, have comparable effect on testosterone glucuronidation. The rate of glucuro nidation was similar on addition of the wine sample once the ethanol had been removed, indicating that it was likely to be the phenolic compounds that caused inhibition. Further studies revealed that etha nol had no effect at the concentrations found in the added wine sample. However, at higher concentra tions of ethanol the UGT2B17 enzyme activity was reduced.

Ethanol has been linked to increased testosterone and aggression in male hamsters and increased testosterone in rat brain. From our results, the effects of alcohol on UGT2B17 are unlikely to account for the increase in testosterone, unless extremely high doses are consumed. Several of the individual wine phenolic compounds inhibited the glucuronidation of testosterone at different efficiencies. The maximum inhibition was observed for quercetin, followed by 4 ethylphenol and caffeic acid. The serum concentrations of phenolic compounds that are commonly found in wine can be increased through supplementation such as with quercetin. In one study, after supplementation, 1. 5 uM quercetin levels in plasma were reported.

This concentration of quer cetin affected a 9% reduction in UGT2B17 activity des pite Drug_discovery a high concentration of testosterone at 20 uM. The reported mean level of serum testosterone in adult males is 35. 9 nM. Given the inhibition is competitive. these much lower concentrations of testosterone should result in higher inhibition of UGT2B17 by quercetin. Fu ture studies are warranted to investigate the effects of red wine and its components at physiological levels of testosterone.