State Key Laboratory of Food Science and Technology & College of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
State Key Laboratory of Food Science and Technology & College of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China.
Int J Biol Macromol. 2021 Aug 1;184:843-856. doi: 10.1016/j.ijbiomac.2021.06.075. Epub 2021 Jun 16.
In this study, the inhibitory activities of eight caffeoylquinic acids (CQAs) against xanthine oxidase (XOD) in vitro were investigated, and the interaction mechanisms between each compound and XOD were studied. HPLC and fluorescence spectra showed that the inhibitory activities of dicaffeoylquinic acids (diCQAs) were higher than that of monocaffeoylquinic acids (monoCQAs), due to the main roles of hydrophobic interaction and hydrogen bond between XOD and diCQAs. Both the binding constant and the lowest binding energy data indicated that the affinities of diCQAs to XOD were stronger than that of monoCQAs. Circular dichroism showed that the structure of XOD was compacted with the increased of α-helix content, resulting in decreased enzyme catalytic activity. Molecular docking revealed that CQAs preferentially bind to the flavin adenine dinucleotide region in XOD. These results provided the mechanisms of CQAs on inhibiting XOD and the further utilization of CQAs as XOD inhibitors to prevent hyperuricemia.
本研究考察了 8 种绿原酸（CQAs）对黄嘌呤氧化酶（XOD）的体外抑制活性，并研究了各化合物与 XOD 的相互作用机制。HPLC 和荧光光谱表明，二咖啡酰奎宁酸（diCQAs）的抑制活性高于一咖啡酰奎宁酸（monoCQAs），这是由于 XOD 与 diCQAs 之间主要存在疏水相互作用和氢键。结合常数和最低结合能数据均表明，diCQAs 与 XOD 的亲和力强于 monoCQAs。圆二色性表明 XOD 的结构变紧凑，α-螺旋含量增加，导致酶催化活性降低。分子对接表明 CQAs 优先结合 XOD 中的黄素腺嘌呤二核苷酸区域。这些结果为 CQAs 抑制 XOD 的机制提供了依据，并为进一步利用 CQAs 作为 XOD 抑制剂预防高尿酸血症提供了理论依据。
