Jiang Lili, Wang Zhen, Wang Xiaoyu, Wang Shujuan, Cao Jun, Liu Yong
School of Life and Pharmaceutical Sciences, Dalian University of Technology 2 Dagong Road, Liaodongwan New District Panjin 124221 China
Department of Occupational and Environmental Health, Dalian Medical University No. 9 W. Lvshun South Road Dalian 116044 China
RSC Adv. 2020 Jan 29;10(8):4529-4537. doi: 10.1039/c9ra09028b. eCollection 2020 Jan 24.
Due to their association with type 2 diabetes mellitus treatment, α-glucosidase inhibitors have attracted increasing attention of researchers. In this study, we systemically investigated the kinetics and inhibition mechanism of piceatannol on α-glucosidase. Enzyme kinetics analyses showed that piceatannol exhibited strong inhibition on α-glucosidase in a non-competitive manner. Spectroscopy analyses indicated that piceatannol could bind with α-glucosidase to form complexes high affinity. Further, computational molecular dynamics and molecular docking studies validated that the binding of piceatannol was outside the catalytic site of α-glucosidase, which would induce conformational changes of α-glucosidase and block the entrance of substrate, causing declines in α-glucosidase activities. Our results provide useful information not only for the inhibition mechanism of piceatannol against α-glucosidase but also for a novel target site for developing novel α-glucosidase inhibitors as potential therapeutic agents in the treatment of type 2 diabetes mellitus.
由于α-葡萄糖苷酶抑制剂与2型糖尿病治疗相关，它们已引起研究人员越来越多的关注。在本研究中，我们系统地研究了白皮杉醇对α-葡萄糖苷酶的动力学和抑制机制。酶动力学分析表明，白皮杉醇以非竞争性方式对α-葡萄糖苷酶表现出强烈抑制作用。光谱分析表明，白皮杉醇可与α-葡萄糖苷酶结合形成高亲和力复合物。此外，计算分子动力学和分子对接研究证实，白皮杉醇的结合位点在α-葡萄糖苷酶催化位点之外，这会诱导α-葡萄糖苷酶构象变化并阻断底物进入，导致α-葡萄糖苷酶活性下降。我们的结果不仅为白皮杉醇对α-葡萄糖苷酶的抑制机制提供了有用信息，也为开发新型α-葡萄糖苷酶抑制剂作为治疗2型糖尿病的潜在治疗药物提供了新的靶点。
