Department of Toxicology, NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Free Radic Biol Med. 2011 Dec 1;51(11):2118-23. doi: 10.1016/j.freeradbiomed.2011.09.013. Epub 2011 Sep 17.
During the scavenging of free radicals flavonoids are oxidized to electrophilic quinones. Glutathione (GSH) can trap these quinones, thereby forming GSH-flavonoid adducts. The aim of this study was to compare the stability of the GSH-flavonoid adduct of 7-mono-O-(β-hydroxyethyl)rutoside (monoHER) with that of quercetin. It was found that GSH-quercetin reacts with the thiol N-acetyl-L-cysteine (NAC) to form NAC-quercetin, whereas GSH-monoHER does not react with NAC. In addition, the adduct of the monoHER quinone with the dithiol dithiothreitol (DTT) is relatively stable, whereas the DTT-quercetin adduct is readily converted into quercetin and DTT disulfide. These differences in reactivity of the thiol-flavonoid adducts demonstrate that GSH-monoHER is much more stable than GSH-quercetin. This difference in reactivity was corroborated by molecular quantum chemical calculations. Thus, although both flavonoid quinones are rapidly scavenged by GSH, the advantage of monoHER is that it forms a stable conjugate with GSH, thereby preventing a possible spread of toxicity. These findings demonstrate that even structurally comparable flavonoids behave differently, which will be reflected in the biological effects of these flavonoids.
在清除自由基的过程中，类黄酮被氧化为亲电醌。谷胱甘肽（GSH）可以捕获这些醌，从而形成 GSH-类黄酮加合物。本研究的目的是比较 7-单-O-(β-羟乙基)芦丁（单 HER）与槲皮素的 GSH-类黄酮加合物的稳定性。结果发现，GSH-槲皮素与硫醇 N-乙酰-L-半胱氨酸（NAC）反应形成 NAC-槲皮素，而 GSH-单 HER 不与 NAC 反应。此外，单 HER 醌与二硫醇二硫苏糖醇（DTT）的加合物相对稳定，而 DTT-槲皮素加合物容易转化为槲皮素和 DTT 二硫化物。这些硫醇-类黄酮加合物反应性的差异表明，GSH-单 HER 比 GSH-槲皮素稳定得多。这种反应性差异得到了分子量子化学计算的证实。因此，尽管两种类黄酮醌都被 GSH 迅速清除，但单 HER 的优势在于它与 GSH 形成稳定的共轭物，从而防止毒性可能扩散。这些发现表明，即使结构相似的类黄酮也表现出不同的行为，这将反映在这些类黄酮的生物学效应中。
