School of Materials Science & Engineering, Beijing Institute of Fashion Technology, Beijing 100029, PR China.
Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, PR China.
Int J Biol Macromol. 2017 Aug;101:32-39. doi: 10.1016/j.ijbiomac.2017.03.072. Epub 2017 Mar 18.
The α-glucosidase inhibitor is of interest to researchers due to its association with type-2 diabetes treatment. Hesperetin is a flavonoid with natural antioxidant properties. This paper presents an evaluation on the effects of hesperetin on α-glucosidase via inhibitory kinetics using a Molecular Dynamics (MD) simulation integration method. Due to the antioxidant properties of hesperetin, it reversibly inhibits α-glucosidase in a slope-parabolic mixed-type manner (IC=0.38±0.05mM; K=0.23±0.01mM), accompanied by tertiary structural changes. Based on computational MD and docking simulations, two hesperetin rings interact with several residues near the active site on the α-glucosidase, such as Lys155, Asn241, Glu304, Pro309, Phe311 and Arg312. This study provides insight into the inhibition of α-glucosidase by binding hesperetin onto active site residues and accompanying structural changes. Hesperetin presents as a potential agent for treating α-glucosidase-associated type-2 diabetes based on its α-glucosidase-inhibiting effect and its potential as a natural antioxidant.
α-葡萄糖苷酶抑制剂因其与 2 型糖尿病治疗的相关性而引起研究人员的关注。橙皮素是一种具有天然抗氧化特性的类黄酮。本文通过分子动力学（MD）模拟整合方法，对橙皮素通过抑制动力学对 α-葡萄糖苷酶的影响进行了评估。由于橙皮素的抗氧化特性，它以斜率抛物线混合抑制型（IC=0.38±0.05mM；K=0.23±0.01mM）可逆地抑制 α-葡萄糖苷酶，同时伴随着三级结构的变化。基于计算 MD 和对接模拟，橙皮素的两个环与 α-葡萄糖苷酶活性部位附近的几个残基相互作用，如 Lys155、Asn241、Glu304、Pro309、Phe311 和 Arg312。这项研究提供了对橙皮素结合到活性部位残基并伴随结构变化抑制 α-葡萄糖苷酶的深入了解。橙皮素具有抑制 α-葡萄糖苷酶的作用，同时也具有天然抗氧化剂的潜力，因此有望成为治疗与 α-葡萄糖苷酶相关的 2 型糖尿病的潜在药物。
