In silico Assessment of the Interaction of the Natural Compound Zeaxanthin with Insulin, Glucocorticoid, and GLP-1 Receptors Associated with Type 2 Diabetes

OpenAlex · İngilizce

Type 2 diabetes mellitus (T2DM), developing because of insulin resistance in peripheral tissues due to pancreatic β-cell dysfunction, chronic metabolic disorder characterized by persistent hyperglycaemia. This pathological state is associated with the impairment of insulin signalling cascades, along with metabolic stress imposed on glucocorticoid and GLP-1 receptors and the perturbation of glucose homeostasis. In this study, interaction potential of the carotenoid pigment zeaxanthin, extracted from natural origins such as microalgae, on insulin, glucocorticoid, and GLP-1 target receptors associated with T2DM was evaluated by employing in silico molecular modelling approaches. Zeaxanthin binding affinities for selected glucocorticoid, insulin, and GLP-1 receptors were computed using the molecular docking method, in comparison with structurally similar natural bioactive compounds and synthetic inhibitors. Molecular dynamics simulations were performed to assess the structural stability of the receptor–ligand complexes that achieved the best conformation over time. Zeaxanthin demonstrated binding energies of -9.9, -6.1 and -8.4 kcal/mol in the INSR, GR, and GLP1, respectively, at a grid size of 30 Å. Similarly, the binding affinities of other ligands structurally analogous to zeaxanthin were comparable to synthetic inhibitors and exhibited stronger binding interactions, supporting zeaxanthin's biological potential. Our findings highlight the potential of natural zeaxanthin as a versatile, targeted natural agent for alternative therapeutic strategies in chronic T2DM. In line with the findings demonstrating zeaxanthin’s potential to reduce insulin resistance within the scope of this study, our preliminary results suggest that zeaxanthin represents a promising lead compound of natural origin with multi-target activity, capable of enhancing insulin sensitivity and regulating glucose homeostasis as part of alternative treatment strategies for T2DM.