Bioavailability of isoflavones and biological activity of major isoflavone metabolites

大豆异黄酮的摄入与广泛的有益健康的影响有关。由于异黄酮在肠道微生物菌群和肝脏中广泛代谢，因此此类效应可能是暴露于母体化合物或代谢物的结果。最近的研究表明，（异）黄酮类化合物的糖结合对这些化合物的吸收和生物利用度有重要影响，但在肠道和肝脏中形成代谢产物的后果尚不清楚。关于主要相关代谢物的生物活性也知之甚少。在本项目中，将在一项具有良好对照交叉设计的人类干预研究中确定一种大豆苷元（大豆苷元）与一种大豆糖缀合物（丙二酰-大豆苷）相比的生物利用度和药代动力学。一个主要目标是确定药代动力学行为的差异是否会影响这些化合物的代谢。此外，大豆苷元和染料木素的主要相关代谢产物的生物活性将通过使用分离的代谢产物离体研究主要代谢产物的抗氧化和促氧化能力、遗传毒性潜力以及雌激素效能来研究。

The intake of soy isoflavones has been associated with a wide range of beneficial health effects. Since isoflavones are extensively metabolized by the gut microflora and in the liver, such effects may be a consequence of exposure to either the parent compounds or the metabolites. Recent studies show that sugar-conjugation of (iso)flavonoids have an important influence on the absorption and bioavailability of these compounds, but the consequences for the formation of metabolites in the gut and in the liver are unclear. Also little is in known about the biological activity of major relevant metabolites. In this project the bioavailability and the pharmacokinetics of an isoflavone aglycone (daidzein) in comparison to an isoflavone sugar conjugate (malonyl-daidzin) will be determined in a human intervention study with a well controlled cross-over design. A major goal is to establish wether, if differences in the pharmacokinetic behavior have an influence on the metabolism of these compounds. Furthermore, the biological activity of the major relevant metabolites of daidzein and genistein will be investigated by studying the anti- and pro-oxidant capacity, the genotoxic potential as well as the estrogenic potency of the major metabolites ex vivo by using of the isolated metabolites.