异甘草素抑制α-葡萄糖苷酶的分子机制  

Inhibitory Mechanism of Isoliquiritigenin against α-Glucosidase

作　　者：韩芬霞[1] 范新景[2] 耿升[2] 娄文娟[2] 梁桂兆[3] 刘本国[2] HAN Fenxia;FAN Xinjing;GENG Sheng;LOU Wenjuan;LIANG Guizhao;LIU Benguo(School of Animal Science and Technology,Henan Institute of Science and Technology,Xinxiang 453003,China;School ofFood Science,Henan Institute of Science and Technology,Xinxiang 453003,China;Key Laboratory of Biorheological Scienceand Technology,Ministry of Education,Bioengineering College,Chongqing University,Chongqing 400044,China)

机构地区：[1]河南科技学院动物科技学院,河南新乡453003 [2]河南科技学院食品学院,河南新乡453003 [3]重庆大学生物工程学院,生物流变科学与技术教育部重点实验室,重庆400044

出　　处：《食品科学》2019年第15期37-42,共6页Food Science

基　　金：国家自然科学基金面上项目(31771941);河南省高等学校重点科研项目(15A230001)

摘　　要：α-葡萄糖苷酶活性与糖尿病患者的餐后血糖水平有重要关联,寻找食源性的α-葡萄糖苷酶抑制剂是当前功能性食品研究的热点。异甘草素是甘草的重要活性成分,相关研究表明甘草提取物具有α-葡萄糖苷酶抑制活性,推测与异甘草素有关。鉴于此,本实验通过酶抑制、荧光猝灭以及分子对接等方法研究异甘草素抑制α-葡萄糖苷酶活性的机制。结果表明,异甘草素以竞争性与非竞争性相混合的方式抑制α-葡萄糖苷酶,其抑制效果明显优于阿卡波糖。荧光猝灭分析结果表明在疏水作用力驱动下异甘草素可与α-葡萄糖苷酶结合生成复合物,结合位点数为1。分子对接结果验证了相关实验结论:异甘草素位于酶的疏水口袋中,与残基Asp202和Arg400以氢键结合,并与周围众多的疏水残基存在疏水作用,共同维持该复合物结构。本研究对于开发新型的食源性α-葡萄糖苷酶抑制剂、推动异甘草素在功能性食品和医药领域的应用具有一定的参考意义。Developing food-derived α-glucosidase inhibitors is one of the most important research topics in the area of functional food because α-glucosidase is closely related to postprandial glucose levels in diabetic patients. It has been reported that an extract of liquorice has α-glucosidase-inhibitory activity, which may be partly attributed to the presence of isoliquiritigenin as one of the major bioactive components in liquorice. Given this background, the α-glucosidase-inhibitory mechanism of isoliquiritigenin was investigated by using enzyme inhibition measurement, fluorescence quenching and molecular docking in the present study. It was found that isoliquiritigenin inhibited α-glucosidase in a mixed competitive and noncompetitive mode, and its performance was superior to that of acarbose. The fluorescence quenching analysis showed that under the action of hydrophobic forces, isoliquiritigenin and α-glucosidase could combine with each other to form a complex with one binding site. The molecular docking results coincided with the experimental results. Isoliquiritigenin,located in the hydrophobic pocket of α-glucosidase, formed hydrogen bonds with Asp202 and Arg400, and interacted with the many surrounding hydrophobic residues by hydrophobic forces, thereby maintaining the structure of the complex.These obtained results are helpful to develop novel food-derived α-glucosidase inhibitors and promote the application of isoliquiritigenin in the fields of functional food and medicine.

关 键 词：异甘草素 Α-葡萄糖苷酶 抑制 荧光光谱 分子对接 

分 类 号：R284.1[医药卫生—中药学]