杨梅素和二氢杨梅素对α-葡萄糖苷酶的抑制作用及机理研究  

Inhibition effects and mechanisms of myricetin and dihydromyricetin on c-amy lase

作　　者：汤萌 阿布里孜·阿不都热合曼 阿达来提·阿布都热西提 张春子 马小燕 马晓丽[1] TANG Meng;ABDURAHMAN Abliz;ABUDUREXITI Adalaiti;ZHANG Chunzi;MA Xiaoyan;MA Xiaoli(College of Pharmacy,Xinjiang Medical Unitersity,Urumgi 830011,Xivjiang,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011

出　　处：《化学研究》2025年第1期57-64,共8页Chemical Research

基　　金：自治区天山英才青年拔尖人才项目(2022TSYCCX0104);新疆特色药材提取物新靶标新作用机制研究(2022A03007-3)。

摘　　要：为研究天然的食源性的小分子α-葡萄糖苷酶抑制剂,采用酶抑制动力学、光谱和分子对接技术研究了杨梅素和二氢杨梅素对α-葡萄糖苷酶的抑制作用及作用机制。结果显示,杨梅素和二氢杨梅素对α-葡萄糖苷酶有良好的抑制作用,半数抑制浓度(IC_(50))分别为71.00μmol·L^(-1)和30.63μmol·L^(-1),二者对酶的抑制作用都是可逆的,杨梅素对酶的抑制作用为非竞争性抑制,二氢杨梅素对酶的抑制作用为竞争性抑制。荧光猝灭结果显示杨梅素和二氢杨梅素与α-葡萄糖苷酶产生静态猝灭。三维荧光光谱结果显示杨梅素和二氢杨梅素都可以使得α-葡萄糖苷酶的光谱特征峰强度减弱。圆二色谱结果表示杨梅素和二氢杨梅素可以改变α-葡萄糖苷酶的二级结构。多光谱分析结果表明,杨梅素对α-葡萄糖苷酶的抑制作用弱于二氢杨梅素。分子对接结果表示杨梅素和二氢杨梅素都可以与α-葡萄糖苷酶的氨基酸残基之间形成氢键和疏水作用力。研究结果可为2型糖尿病的新药开发提供了理论基础。In order to study the natural foodborne small moleculeα-glucosidase inhibitors,the inhibitory effect of myricetin and dihydromyricetin onα-glucosidase and its mechanism were studied by enzyme inhibition kinetics,spectroscopy and molecular docking techniques.The results showed that myricetin and dihydromyricetin had a good inhibitory effect onα-glucosidase,with the median inhibitory concentration(IC_(50))of 71.00μmol·L^(-1) and 30.63μmol·L^(-1),respectively.The inhibitory effect of myricetin onα-glucosidase was reversible.The inhibitory effect of myricetin on enzyme was non-competitive,and the inhibitory effect of dihydromyricetin on enzyme was competitive.Fluorescence quenching results showed that myricetin and dihydromyricetin andα-glucosidase produced static quenching.Three-dimensional fluorescence spectra showed that both myricetin and dihydromyricetin could reduce the spectral peak intensity ofα-glucosidase.The results of circular dichroic chromatography showed that myricetin and dihydromyricetin could change the secondary structure ofα-glucosidase.The results of multispectral analysis showed that the inhibitory effect of myricetin onα-glucosidase was weaker than that of dihydromyricetin.Molecular docking results showed that both myricetin and dihydromyricetin could form hydrogen bonds and hydrophobic forces with amino acid residues ofα-glucosidase.The results can provide a theoretical basis for the development of new drugs for type 2 diabetes.

关 键 词：Α-葡萄糖苷酶 杨梅素 二氢杨梅素 光谱 分子对接 

分 类 号：O621.4[理学—有机化学]