黄酮型邻苯醌消除食源性晚期糖化终末产物的机制研究

Dietary advanced glycation end products (AGEs) have aroused great attention because of their potential hazard towards human beings. AGEs inhibitors can significantly inhibit the formation of AGEs in food systems; however they have no effect on the existing AGEs. o-Benzoquinones which are obtained from flavonoids oxidation (flavonoid o-benzoquinones) can directly react with AGEs leading to the elimination of existing AGEs, therefore minimizing the potential hazard of dietary AGEs. In this project, the relationships between the structure of flavonoid o-benzoquinones and their AGEs elimination ability or their stability are investigated. The structure-activity relationship study on the AGEs elimination effect of flavonoid o-benzoquinones was performed through the quantitative structure activity relationship (QSAR). The interaction of flavonoid o-benzoquinones with free-AGEs, peptide-AGEs and protein-AGEs are studied. Related kinetic models are established. Isotope labeled technique is applied to investigate the pathway of flavonoid o-benzoquinones reaction with AGEs. The structures of elimination products are analyzed. The elimination mechanisms of flavonoid o-benzoquinones on AGEs are illuminated. This research will provide strategies to eliminate the existing AGEs in food system, thus minimizing or eliminating the potential hazard of AGEs.

食源性晚期糖化终末产物（AGEs）对人体的潜在危害性已受到广泛关注，AGEs抑制剂虽能有效降低食品体系AGEs的终含量，但对食品体系中已经存在的AGEs却并无作用。为最大程度降低食源性AGEs的危害，本项目提出利用天然黄酮氧化生成的含邻苯二醌结构的醌类物质（黄酮型邻苯醌）消除食源性AGEs的新思路，重点研究黄酮型邻苯醌的结构与其稳定性及AGEs消除活性之间的关系，构建黄酮型邻苯醌消除AGEs的结构与反应性量化模型。考察黄酮型邻苯醌与单体-AGEs、肽-AGEs复合物以及蛋白质-AGEs复合物的相互作用，构建相关的动力学模型，通过同位素标记跟踪分析黄酮型邻苯醌和AGEs的作用路径，深入研究消除产物的结构特性，阐明黄酮型邻苯醌消除AGEs的作用机制。本研究可以有效消除食品体系中已存在的AGEs，从而进一步降低或者去除食源性AGEs带来的潜在危害。

食源性晚期糖化终末产物（AGEs）对人体的潜在危害性已受到广泛关注，AGEs抑制剂虽能有效降低食品体系AGEs的终含量，但对食品体系中已经存在的AGEs却并无作用。黄酮型邻苯醌具有潜在的AGEs消除效能且应用安全性较好，具有作为AGEs消除剂在食品中应用的可能。本项目采用循环伏安技术考察了黄酮型邻苯醌对AGEs的消除作用，阐明了醌类物质结构与其AGEs消除活性之间的关联，明晰了醌类物质对不同AGEs的消除作用，考察了食品加工条件下黄酮型邻苯醌对模拟体系AGEs的消除效率；采用高分辨质谱等技术明确了消除产物结构特性，阐明了黄酮型邻苯醌消除AGEs相关机制；利用人工胃液及人工小肠液考察了消除产物的体外消化稳定性。研究表明，醌环上给电子取代基削弱醌类物质对AGEs的消除效率，反之拉电子取代基增强醌类物质对AGEs的消除效率，此外取代基的空间位阻也将显著影响醌类物质对AGEs的消除效率；醌类对吡咯素的消除效率大于其对羧甲基赖氨酸（CML）的消除效率及其对羧乙基赖氨酸（CEL）的消除效率；酸性条件会促进氨基质子化进而降低其亲核性，因此中性或碱性条件下醌类物质对AGEs的消除效率显著高于酸性条件；AGEs-醌加和物是以醌类物质的形式存在的，醌类物质先与AGEs作用形成无色的胺-酚加和物，而后迅速被氧气氧化形成粉色的胺-醌加和物；体外消化实验表明，经人工胃液及小肠液消化后，体系中CML含量会显著降低，且该降低阶段主要发生在人工胃液作用阶段。本项目研究成果丰富了食源性AGEs含量控制领域的理论知识，为前瞻性地控制食源性AGEs的潜在危害性提供了科学依据。