Faculty of Biological Science and Technology, Department of Cell and Molecular Biology & Microbiology, University of Isfahan, Isfahan, Iran.
Faculty of Biological Science and Technology, Department of Cell and Molecular Biology & Microbiology, University of Isfahan, Isfahan, Iran.
Int J Biol Macromol. 2022 Sep 30;217:714-730. doi: 10.1016/j.ijbiomac.2022.07.086. Epub 2022 Jul 14.
Flavonoid glycosides (FGs) appear to be good candidates for controlling blood glucose levels, so regular consumption of vegetables/fruits rich in FGs may prevent the consequences of type 2 diabetes (DM). Inhibition of digestive enzymes using natural FGs is a suitable dietary tool to regulate the hydrolysis of polysaccharides and overcome hyperglycemia. The aim of the current research is to find FGs that can effectively inhibit the digestive enzymes α-glucosidase (α-Gl) and α-amylase (α-Am). Accordingly, twenty-three FGs were selected and filtered through docking-based virtual screening. Based on the molecular docking and molecular dynamics (MD) simulation, among the 23 selected FGs, nicotiflorin and swertisin significantly inhibited α-Gl and α-Am, respectively. In vitro analysis revealed the inhibitory capacity of nicotiflorin on α-Gl was equal to IC50 at 0.148 mg/ml and the inhibitory activity of swertisin on α-Am was equal to IC50 at 1.894 mg/ml. It was found that nicotiflorin and swertisin act much like as a competitive inhibitor on α-Gl and α-Am, respectively. Furthermore, the fluorescence intensity of both enzymes decreased after interaction with two FGs. FT-IR and scanning electron microscopy (SEM) measurements suggested that the interactions could alter the conformation and microenvironment of the enzymes. Moreover, in vivo evaluation showed that the administration of nicotiflorin and swertisin can alleviate the blood glucose level of rats compared to the starch group (p < 0.05). The findings highlight that nicotiflorin and swertisin can be considered as possible inhibitors in treating diabetes mellitus via digestive enzymes inhibition.
类黄酮糖苷（FGs）似乎是控制血糖水平的良好候选物，因此经常食用富含 FGs 的蔬菜/水果可能预防 2 型糖尿病（DM）的后果。使用天然 FGs 抑制消化酶是调节多糖水解和克服高血糖的合适饮食工具。目前研究的目的是找到可以有效抑制消化酶α-葡萄糖苷酶（α-Gl）和α-淀粉酶（α-Am）的 FGs。因此，选择了 23 种 FGs 并通过基于对接的虚拟筛选进行了筛选。基于分子对接和分子动力学（MD）模拟，在所选择的 23 种 FGs 中，野靛碱和獐牙菜苦苷分别显著抑制了α-Gl 和α-Am。体外分析表明，野靛碱对α-Gl 的抑制能力等于 IC50 在 0.148mg/ml，獐牙菜苦苷对α-Am 的抑制活性等于 IC50 在 1.894mg/ml。发现野靛碱和獐牙菜苦苷分别对α-Gl 和α-Am 的作用类似于竞争性抑制剂。此外，两种 FGs 相互作用后，两种酶的荧光强度均降低。FT-IR 和扫描电子显微镜（SEM）测量表明，相互作用可以改变酶的构象和微环境。此外，体内评价表明，与淀粉组相比，野靛碱和獐牙菜苦苷的给药可以降低大鼠的血糖水平（p<0.05）。研究结果表明，野靛碱和獐牙菜苦苷可以通过抑制消化酶被认为是治疗糖尿病的潜在抑制剂。
