含邻苯二酚结构的多酚对晚期糖基化终末产物抑制与消除的双效机制研究

Dietary advanced glycation end products (AGEs) have been paid more and more attention since they are proved to be related with many chronic diseases. In order to reduce the hazard of dietary AGEs, the AGEs levels in foods should be cut down. Extensively studies were paid attention to the inhibition effects of additives on AGEs formation; however, additives may also have the potential elimination effect on AGEs which is ignored by food researchers. The polyphenols which contain a catechol moiety could react with AGEs to eliminate the existing AGEs. In this project, the mechanism of polyphenols with catechol moieties reaction with AGEs is investigated. Related kinetic models are established. The stability and bioavailability of the product obtained by polyphenol reaction with AGEs are studied. Inhibition effects of polyphenols with catechol moieties on AGEs formation are investigated in the presence of quinone trapping agents. Carbon labeling technology is applied for the study of AGEs formation pathways. The inhibition and elimination mechanism of polyphenols with catechol moieties on AGEs levels will be setup, which will supply significant and important reference on dietary AGEs control by the addition of exogenous additives.

食源性晚期糖期化终末产物（AGEs）对人体的危害性越来越受到关注，减少食品中AGEs的含量是降低AGEs对人体危害的重要方法。针对当前对已存在的AGEs没有有效的消除措施的现状，本项目提出含邻苯二酚结构的多酚消除食源性AGEs的研究新思路，重点研究含邻苯二酚结构的多酚与AGEs相互作用，建立AGEs消除的动力学模型，考察消除产物的稳定性及生物利用度，阐明含邻苯二酚结构的多酚对AGEs的消除机制；研究在醌类捕获剂存在下，含邻苯二酚结构的多酚对AGEs生成的抑制规律，通过碳标记技术跟踪分析AGEs的生成途径，阐明对AGEs生成的抑制机理。通过对比分析，揭示含邻苯二酚结构的多酚对AGEs抑制与消除的双效作用，研究AGEs含量的动态变化规律及反应动力学，阐明含邻苯二酚结构的多酚对AGEs的抑制与消除的双效机制。为通过外源添加物控制食源性AGEs危害性提供有用的参考数据与新的研究思路。

食源性晚期糖期化终末产物（AGEs）对人体的危害性越来越受到关注，减少食品中AGEs的含量是降低AGEs对人体危害的重要方法，含邻苯二酚结构的多酚具备抑制与消除AGEs的潜能。本项目采用同位素标记法建立了数学模型，通过监测模拟体系中AGEs含量的动态变化规律，系统地研究了不同种类的糖（葡萄糖、果糖、乳糖）以及加工条件（浓度、pH）下代表性多酚对AGEs生成的抑制规律以及对AGEs的捕获效能；通过电化学以及酶法，分别研究了AGEs结构、外界条件及竞争性基团存在等条件下含邻苯二酚结构的多酚对AGEs消除的影响，并通过量子化学方法对结果进行了分析验证；考察了不同外界环境条件下，AGEs消除产物的稳定性。. 研究结果表明，含邻苯二酚结构的多酚对AGEs的抑制与捕获能力与多酚添加浓度以及体系pH有关，与模拟体系糖种类无关；醌类物质对AGEs及其他食品体系常见亲核物质的消除能力，主要与醌类物质的亲电能力以及AGEs或亲核物质的亲核能力有关，量子化学数据进一步佐证了这结论；此外，消除效率还与醌类物质及AGEs或亲核物质的溶解性等密切相关；明晰了咖啡酸与糖化蛋白的共价以及非共价相互作用情况，并通过细胞实验验证了上述相互作用产物的生物利用情况，结果表明，咖啡酸不仅可以直接通过其抗氧化活性抑制AGEs诱导的细胞炎症反应，还可能通过与AGEs发生相互作用，进而阻断AGEs与其受体RAGE的特异性结合。该研究结论是对目前多酚抑制AGEs生成理论的有力补充，能够较好地解决食品加工过程产品安全性的基础科学问题。