College of Ocean Food and Biological Engineering, Jimei University, Xiamen, China.
Fujian Provincial Key Laboratory of Food Microbiology and Enzyme Engineering, Xiamen, China.
J Food Biochem. 2022 Oct;46(10):e14370. doi: 10.1111/jfbc.14370. Epub 2022 Aug 9.
The inhibition of aldose reductase is an effective strategy to alleviate symptoms of diabetic complications. The p-coumaric acid ethyl ester (p-CAEE) was taken as an example to investigate the inhibition of aldose reductase from p-coumaric acid derivations. The results showed p-CAEE strongly inhibited aldose reductase with the half inhibitory concentration of 1.92 μM, following the noncompetitive manner with a K value of 0.94 μM. After binding with p-CAEE, the enzyme showed increased β-sheet content, and the α-helix content, random coil content, and intrinsic fluorescence strength decreased. p-CAEE bonded with aldose reductase at the anionic, hydrophobic, and selective pockets of the enzyme, via hydrogen bond and hydrophobic interactions with Thr113, Cys80, Trp111, and Leu300, etc. The strong inhibition was related to the high oil-water partition coefficient and special esterify group. This study provides new information to develop aldose reductase inhibitors from p-coumaric acid derivations. PRACTICAL APPLICATIONS: Inhibition of aldose reductase is an effective strategy to alleviate and control the symptoms of diabetic complications. In this study, it has been shown that p-coumaric acid ethyl ester could strongly inhibit the aldose reductase. In addition, the inhibition of aldose reductase was been correlated with structures and oil-water partition coefficients of p-coumaric acid derivatives. It provides a theoretical basis for the development of effective aldose reductase inhibitors.
醛糖还原酶的抑制作用是缓解糖尿病并发症症状的有效策略。以对羟基肉桂酸乙酯（p-CAEE）为例，研究了对羟基肉桂酸衍生物对醛糖还原酶的抑制作用。结果表明，p-CAEE 强烈抑制醛糖还原酶，其半数抑制浓度为 1.92μM，表现为非竞争性抑制，K 值为 0.94μM。与 p-CAEE 结合后，酶的β-折叠含量增加，α-螺旋含量、无规则卷曲含量和固有荧光强度降低。p-CAEE 与醛糖还原酶结合在酶的阴离子、疏水性和选择性口袋中，通过氢键和疏水相互作用与 Thr113、Cys80、Trp111 和 Leu300 等结合。强抑制作用与高油水分配系数和特殊酯化基团有关。本研究为开发对羟基肉桂酸衍生物的醛糖还原酶抑制剂提供了新的信息。实际应用：醛糖还原酶的抑制作用是缓解和控制糖尿病并发症症状的有效策略。在这项研究中，已经表明对羟基肉桂酸乙酯可以强烈抑制醛糖还原酶。此外，醛糖还原酶的抑制作用与对羟基肉桂酸衍生物的结构和油水分配系数有关。它为开发有效的醛糖还原酶抑制剂提供了理论依据。
