甜菊醇、异甜菊醇抑制α-葡萄糖苷酶和HMG-CoA还原酶的分子机制研究

本文研究了甜菊醇、异甜菊醇抑制高血糖、高血脂代谢关键酶α-葡萄糖苷酶、HMG-CoA还原酶活性的分子机制。采用分光光度法测定甜菊醇、异甜菊醇对α-葡萄糖苷酶、HMG-CoA还原酶抑制率，用双倒数作图法研究甜菊醇、异甜菊醇的酶抑制动力学，利用AutoDock软件对甜菊醇、异甜菊醇与α-葡萄糖苷酶、HMG-CoA还原酶的结合模式进行分析。结果表明:甜菊醇、异甜菊醇对α-葡萄糖苷酶的IC₅₀分别为70.75、49.65 mg/L，采用竞争性与非竞争性相混合的方式抑制α-葡萄糖苷酶；甜菊醇、异甜菊醇对HMG-CoA还原酶的IC₅₀分别为46.29、36.66 mg/L，竞争性抑制HMG-CoA还原酶。分子对接的分析结果表明甜菊醇、异甜菊醇分别位于α-葡萄糖苷酶、HMG-CoA还原酶的疏水口袋中，与多个氨基酸残基结合，并存在疏水作用。本研究对于开发新型的食源性α-葡萄糖苷酶和HMG-CoA还原酶抑制剂，推动甜菊醇、异甜菊醇在食品和医药领域的应用具有一定的参考意义。

Molecular Mechanism of Inhibition of α-Glucosidase and HMG-CoA Reductase Activities by Steviol and Isosteviol

This study focused on the molecular mechanism of inhibition of activities of α-glucosidase and HMG-CoA reductase which were the key enzymes of hyperglycemia and hyperlipidemia by steviol and isosteviol. The inhibition rate of steviol and isosteviol to α-glucosidaseand HMG-CoA reductase was determined by spectrophotometry. The enzyme inhibition kinetics were studied by double reciprocal plot method, and the molecular binding mode was analysised by AutoDock software. The results showed that the IC₅₀ of steviol, isosteviol to α-glucosidase were 70.75 and 49.65 mg/L respectively. The activity of α-glucosidase was inhibited by competitive and non competitive methods. The IC₅₀ of steviol, isosteviol to HMG-CoA reductase were 46.29 and 36.66 mg/L, which competitively inhibited HMG-CoA reductase. The results of molecular docking showed that steviol and isosteviol were located in the hydrophobic pocket of α-glucosidase and HMG CoA reductase, they bind with multiple amino acid residues and have hydrophobic effect. This study would provide theoretical reference for the development of new type inhibitors of foodborne α-glucosidase and HMG-CoA reductase, and the promotion of the application of steviol and isosteviol in food and medicine.