Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, 500 Laureate Way, Kannapolis, NC 28081, United States.
Chem Res Toxicol. 2011 Apr 18;24(4):579-86. doi: 10.1021/tx100457h. Epub 2011 Feb 23.
Methylglyoxal (MGO) is a highly reactive endogenous metabolite derived from several nonenzymatic and enzymatic reactions, and identified as a well-known precursor of advanced glycation end products (AGEs). In the present study, genistein, a naturally occurring isoflavone derived from soy products, demonstrated significant trapping effects of MGO and consequently formed mono- and di-MGO adducts under physiological conditions (pH 7.4, 37 °C). More than 80.0% of MGO was trapped within 4 h, and the trapping efficiency could be up to 97.7% at 24 h. The reaction adducts formed from genistein and MGO under different ratios were analyzed using LC/MS. We also successfully purified and identified the major mono- and di-MGO conjugated adducts of genistein. The NMR data showed that positions 6 and 8 of the A ring of genistein were the major active sites for trapping MGO. We further demonstrated that genistein could effectively inhibit the formation of AGEs in the human serum albumin (HSA)-MGO assay. Two mono-MGO adducts and one di-MGO adduct of genistein were detected in this assay using LC/MS. The di-MGO adduct of genistein became the dominant reaction product during prolonged incubation. Results from this study, as well as our previous findings on (-)-epigallocatechin 3-gallate (EGCG), phloridzin and phloretin, indicate that dietary flavonoids that have the same A ring structure as genistein, EGCG, phloridzin, and phloretin may have the potential to inhibit the formation of AGEs by trapping reactive dicarbonyl species.
甲基乙二醛（MGO）是一种高度反应性的内源性代谢物，源自几种非酶和酶促反应，并被鉴定为晚期糖基化终产物（AGEs）的已知前体。在本研究中，染料木黄酮，一种源自大豆制品的天然异黄酮，在生理条件下（pH7.4，37°C）对 MGO 表现出显著的捕获作用，从而形成单和二 MGO 加合物。在 4 小时内，超过 80.0%的 MGO 被捕获，在 24 小时内，捕获效率可达 97.7%。使用 LC/MS 分析了染料木黄酮与 MGO 在不同比例下形成的反应加合物。我们还成功地纯化和鉴定了染料木黄酮与 MGO 形成的主要单和二 MGO 缀合加合物。NMR 数据表明，染料木黄酮 A 环的 6 位和 8 位是捕获 MGO 的主要活性位点。我们进一步证明，染料木黄酮可以有效抑制人血清白蛋白（HSA）-MGO 测定中 AGEs 的形成。在该测定中，使用 LC/MS 检测到染料木黄酮的两个单-MGO 加合物和一个二-MGO 加合物。在长时间孵育过程中，染料木黄酮的二-MGO 加合物成为主要反应产物。本研究以及我们之前关于（-）-表没食子儿茶素 3-没食子酸酯（EGCG）、根皮苷和根皮素的发现表明，具有与染料木黄酮、EGCG、根皮苷和根皮素相同 A 环结构的膳食类黄酮可能具有通过捕获反应性二羰基化合物来抑制 AGEs 形成的潜力。
