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

Timing of uplift and evolution of the Lüliang Mountains, North China Craton

This study analyses evidence for reformed basin development and basin-mountain coupling associated with development of the Ordos Basin and the Lüliang Mountains, China. Gaining an improved understanding of the timing and nature of uplift and evolution of the Lüliang Mountains is important for the reconstruction of the eastern sedimentary boundary of the Ordos Basin (a major petroliferous basin) as well as for providing insight into the evolution and breakup of the North China Craton (NCC). Based on systematic sampling for fission track analysis, it is suggested that the main phase of uplift of the Lüliang Mountains occurred since later part of the Early Cretaceous. Three evolutionary stages of uplift and development are identified: slow initial uplift (120–65 Ma), accelerated uplift (65–23 Ma), and intensive uplift (23 Ma to present), with the majority of the uplift activity having occurred during the Cenozoic. The history of uplift is non-equilibrium and exhibits complexity in temporal and spatial aspects. The middle and northern parts of the Lüliang Mountains were uplifted earlier than the southern part. The most intensive episode of uplift activity commenced in the Miocene and was associated with a genetic coupling relationship with the eastern neighboring Cenozoic Shanxi Grabens. The uplifting and evolutionary processes of the Lüliang Mountains area since later part of the Early Cretaceous share a unified regional geodynamic setting, which was accompanied by uplift of the Mesozoic Ordos Basin and development of the neighboring Cenozoic Shanxi Grabens. Collectively, this regional orogenic activity is related principally to the far-field effects of both the compression sourced from the southwestern Tibet Plateau and westward subduction of the Pacific Plate in Cenozoic