Human Pancreatic Amylase (HPA) is an important target for prevention and treatment of type 2 diabetes. Acarbose is a currently available drug acting as a HPA inhibitor, but its gastrointestinal side-effects cannot be neglected. Thus, developing novel HPA inhibitors with no side-effects is of great importance. Herein, we adopted a structure-based design approach and discovered a potent HPA inhibitor, malvidin 3-O-arabinoside (M3A), from the natural anthocyanin database. We identified M3A as an effective HPA inhibitor through virtual screening, enzyme activity and enzyme kinetic assays. We reported the structure and activity relationships as both the anthocyanidin core and glucosyl group affected the HPA inhibitory effect of anthocyanins. Molecular dynamics studies indicated that the HPA inhibition of M3A occurred via its binding to the HPA key catalytic residues Arg195 and Asp197 through stable hydrogen bonding. In addition, M3A was found to reduce α-helix fractions and increase β-sheet fractions in CD spectrometry. Further in vivo studies showed that M3A significantly ameliorated the postprandial blood glucose level. Taken together, our results provide new insights into the development of novel HPA inhibitors from natural sources as food supplements for type 2 diabetes.

中文翻译：

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基于天然花青素数据库的2型糖尿病人胰腺淀粉酶抑制剂的基于结构的设计。

人胰腺淀粉酶（HPA）是预防和治疗2型糖尿病的重要靶标。阿卡波糖是目前可作为HPA抑制剂的药物，但其胃肠道副作用不可忽略。因此，开发无副作用的新型HPA抑制剂非常重要。在本文中，我们采用了基于结构的设计方法，并从天然花色苷数据库中发现了一种有效的HPA抑制剂麦维京3-O-阿拉伯糖苷（M3A）。通过虚拟筛选，酶活性和酶动力学分析，我们确定了M3A是有效的HPA抑制剂。我们报告了结构和活性之间的关系，因为花青素核心和葡萄糖基都影响花青素对HPA的抑制作用。分子动力学研究表明，HPA对M3A的抑制作用是通过稳定的氢键与HPA关键催化残基Arg195和Asp197结合而实现的。另外，在CD光谱法中发现M3A减少α-螺旋部分并增加β-折叠部分。进一步的体内研究表明，M3A可以显着改善餐后血糖水平。综上所述，我们的结果为开发天然HPA抑制剂作为2型糖尿病的食品补充剂提供了新的见解。