Abstract
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 μM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.
Highlights
Tea is a cheap and commonly consumed human beverage, often considered a healthy habit [3, 4]
epigallocatechin gallate (EGCG) was searched in the PDB database as a search term, four structures cocrystallized with EGCG and one structure cocrystallized with EGC were acquired, and none of them was related to glucose metabolism
Seventeen chemical structures of ligands containing the flavonoid scaffold were identified by substructure search (Figure 2), and 40 cocrystal structures of proteins with the flavonoid scaffold substructure of EGCG were identified in the PDB (PDB IDs 6MS8, 6G8H, 6AWT, 6AWV, 6AX0, 6DHL, 6F6A, 5WKR, 5WKS, 5J3J, 5F8P, 5JDC, 4MA6, 4D06, 4KZQ, 4C94, 4C9I, 4EH3, 4DEU, 4AWM, 4A87, 3NG5, 3TVQ, 3OOB, 3I52, 3D04, 2KDH, 2NNL, 2UXU, 2C29, 2BRT, 1GP5, 1JNQ, 1JX0, 1JX1, 1FM7, 1FM8, 1JEP, 1EYQ, and 1CGK); the information about these proteins is reported in Table 1. e relationship between these proteins and diabetes was investigated in PubMed
Summary
Tea is a cheap and commonly consumed human beverage, often considered a healthy habit [3, 4]. Green tea has important effects on human health, mainly attributed to its flavonoid-like polyphenols, such as catechins. Compounds in tea can reduce the risk of chronic illnesses including cardiovascular disease, cancer, arthritis, and diabetes [3,4,5,6,7,8]. In addition to blood glucose regulation, DPP4 inhibitors may have extra-glycemic effects such as myocardial protection, lowering blood pressure, reducing the expression of local inflammatory factors, and improving vascular endothelial function [14]. Side effects such as hemolysis, angioedema, and rheumatoid arthritis have been observed [13]. E aim of this study was to identify novel target proteins of EGCG that are relevant to diabetes and provide new data on the relationship between EGCG and glucose metabolism
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