Inhibitory mechanism of sinensetin on α-glucosidase and non-enzymatic glycation: Insights from spectroscopy and molecular docking analyses
Inhibitory mechanism of sinensetin on α-glucosidase and non-enzymatic glycation: Insights from spectroscopy and molecular docking analyses
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DOI：
10.1016/j.ijbiomac.2020.10.174
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发表时间：
2021-01-01
影响因子：
8.2
通讯作者：
Liu, Jianli
中科院分区：
文献类型：
--
作者：
Liu, Dan;Cao, Xiangyu;Liu, Jianli
抑制α-葡萄糖苷酶和非酶糖基化被认为是预防和治疗2型糖尿病及其并发症的有效方法。本研究采用多光谱技术和分子对接技术研究了sinensetin对α-葡萄糖苷酶和非酶糖基化的抑制作用。荧光光谱分析结果表明，sinensetin对α-葡萄糖苷酶的内源荧光具有静态猝灭作用。sinensetin与α-葡萄糖苷酶的结合是一个自发的过程，主要由疏水相互作用驱动。在298 K时，结合常数为（5.70 +/- 0.12）x 10（4）L.mol（-1），结合位点数为1。利用圆二色谱（CD）、红外光谱（FTIR）、同步荧光和三维荧光光谱（3D）等方法研究了sinensetin对α-葡萄糖苷酶构象的影响。分子对接分析表明，sinensetin与α-葡萄糖苷酶的氨基酸残基发生相互作用，阻碍了底物的进入，导致α-葡萄糖苷酶的催化效率降低。糖基化实验表明，sinensetin能稳定牛血清白蛋白（BSA）的结构，与BSA相互作用，抑制二酪氨酸、N '-甲酰犬尿氨酸和晚期糖基化终产物（AGEs）的形成。本研究为西南西汀预防和治疗2型糖尿病及其并发症提供了有益的信息。(C)2020爱思唯尔B. V.保留所有权利。
Inhibition of alpha-glucosidase and non-enzymatic glycation is regarded as an effective method to prevent and treat type 2 diabetes and its complications. In this study, the inhibition of sinensetin on alpha-glucosidase and nonenzymatic glycation was studied with multi-spectroscopic techniques and molecular docking analysis. The results of fluorescence spectroscopy analysis indicated that sinensetin quenched the endogenous fluorescence of alpha-glucosidase in static manner. The binding of sinensetin with alpha-glucosidase was a spontaneous process primarily driven by hydrophobic interaction. At 298 K, the binding constant was (5.70 +/- 0.12) x 10(4) L.mol(-1) and the binding site number was 1. The conformation of alpha-glucosidase was altered by sinensetin, which was revealed by circular dichroism (CD), FTIR spectra, synchronous fluorescence and three-dimensional (3D) fluorescence spectroscopy methods. Molecular docking analysis demonstrated that sinensetin interacted with the amino acid residues of alpha-glucosidase, which might prevent the entrance of substrate, leading to the decrease of catalytic efficiency of alpha-glucosidase. Furthermore, glycation assays showed that sinensetin stabilized the structure of bovine serum albumins (BSA), interacted with BSA, strongly inhibited the formation of dityrosine, N'-formylkynurenine and advanced glycation end products (AGEs). This study provided useful information concerning sinensetin preventing and treating type 2 diabetes and its related complications. (C) 2020 Elsevier B.V. All rights reserved.