Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea.
Institut Pasteur Korea, Seongnam-si, Gyeonggi-do 13488, Korea.
Molecules. 2018 Aug 10;23(8):1998. doi: 10.3390/molecules23081998.
Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (⁻) were isolated from the seeds of Medikus (Fabaceae) and tested for their DPP-IV⁻inhibitory activity. We demonstrated for the first time, that compounds ⁻ inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds ⁻ within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.
二肽基肽酶 IV（DPP-IV）是治疗 2 型糖尿病的新靶点，可降解胰高血糖素样肽 1（GLP-1）和葡萄糖依赖性胰岛素释放肽等肠降血糖素。DPP-IV 抑制剂可缩短 GLP-1 的失活时间，使肠降血糖素能够刺激胰岛素释放，从而对抗高血糖。在我们从药用植物和食物中寻找新的 DPP-IV 抑制剂的过程中，从 Medickus（豆科）的种子中分离出三种黄酮醇糖苷（⁻），并对其 DPP-IV⁻抑制活性进行了测试。我们首次证明，在我们的体外生物测定系统中，化合物 ⁻ 以浓度依赖的方式抑制 DPP-IV 活性。此外，还对化合物 ⁻ 在 DPP-IV 结合口袋内的分子对接实验进行了研究。所有研究的化合物都很容易在 DPP-IV 的活性部位内适应，在低能量构象中，黄酮核心结构具有与 DPP-IV 的催化三联体残基的最佳静电吸引相互作用。
