Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, China.
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Biomed Res Int. 2020 Feb 11;2020:5370759. doi: 10.1155/2020/5370759. eCollection 2020.
Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 M. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.
表没食子儿茶素没食子酸酯 (EGCG) 是绿茶中的一种主要活性成分，具有多种健康益处。它影响葡萄糖代谢，但机制尚不清楚。本研究旨在确定与葡萄糖代谢相关的 EGCG 靶标。EGCG 的核心片段是一种类黄酮。类黄酮支架被用作子结构，在蛋白质数据库中寻找与类黄酮共结晶的蛋白质。通过这种方法在 PubMed 中筛选出与糖尿病相关的已知蛋白质。随后，根据这种方法鉴定出二肽基肽酶 4（DPP4；PDB 5J3J）。通过分子对接评估 EGCG 和 DPP4 之间的相互作用。为了测试 EGCG 和 DPP4 之间相互作用的稳定性，使用 Desmond 软件进行了 100ns 的分子动力学模拟。在体外，抑制 DPP4 活性 50%所需的 EGCG 浓度（IC50 值）为 28.42μM。这些数据为用 EGCG 干预葡萄糖代谢提供了理论依据。
