State Key Laboratory of Food Science and Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, International Joint Research Laboratory for Lipid Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
School of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, China.
J Agric Food Chem. 2021 Dec 22;69(50):15252-15260. doi: 10.1021/acs.jafc.1c06347. Epub 2021 Dec 13.
Inhibition of α-glucosidase activity is closely related to the treatment of type 2 diabetes. However, the potential mechanism by which 4,4-dimethylsterols inhibit α-glucosidase has not been elucidated. In this work, the inhibitory activity and mechanism of 4,4-dimethylsterols against α-glucosidase were studied through kinetic analysis, fluorescence spectroscopy, ultraviolet spectroscopy, circular dichroism, and molecular docking. 4,4-Dimethylsterols showed higher inhibition activity against α-glucosidase than acarbose with an IC value of 0.71 mg/mL and a noncompetitive inhibition type. They could bind to α-glucosidase through van der Waals forces and hydrogen bonds and quench its endofluorescence with a static quenching mechanism. Changes in the secondary structure of α-glucosidase were induced by its binding interaction with 4,4-dimethylsterols. Molecular docking further indicated that a hydrogen bond was generated between OH at the C-3 position of 4,4-dimethylsterols and the α-glucosidase residue Arg-442. This study provides new insights into the potential utilization of 4,4-dimethylsterols as antidiabetic phytochemicals in dietary supplements.
抑制α-葡萄糖苷酶活性与 2 型糖尿病的治疗密切相关。然而，4,4-二甲基甾醇抑制α-葡萄糖苷酶的潜在机制尚未阐明。在这项工作中，通过动力学分析、荧光光谱、紫外光谱、圆二色性和分子对接研究了 4,4-二甲基甾醇对α-葡萄糖苷酶的抑制活性和机制。4,4-二甲基甾醇对α-葡萄糖苷酶的抑制活性高于阿卡波糖，IC 值为 0.71mg/mL，为非竞争性抑制类型。它们可以通过范德华力和氢键与α-葡萄糖苷酶结合，并通过静态猝灭机制猝灭其末端荧光。4,4-二甲基甾醇与α-葡萄糖苷酶的结合相互作用诱导了α-葡萄糖苷酶的二级结构发生变化。分子对接进一步表明，4,4-二甲基甾醇 C-3 位的 OH 与α-葡萄糖苷酶残基 Arg-442 之间形成了氢键。本研究为将 4,4-二甲基甾醇作为膳食补充剂中的抗糖尿病植物化学物质的潜在应用提供了新的见解。
