Eggplant (Solanum spp.) Fruits Dietary Polyphenols Upregulate the Expression of Glucose Transporter Protein in Palmitate-Induced Diabetic Cell Line C2C12

Studies utilizing cell-based systems to investigate plant-based diets for diabetes management are gaining attention due to the adverse effects associated with commercially available drugs. However, the molecular mechanisms underlying the anti-diabetic effects of specific plant-derived products remain inadequately explored. The major aim of our study was to elucidate the molecular mechanisms by which bioactive compounds in the fruit of <i>Solanum</i> spp. influence key proteins associated with type 2 diabetes. The expressions of genes such as glucose transporter protein 4 (<i>GLUT4</i>), myocyte enhancer factor-2 (<i>MEF-2A</i>), and nuclear respiratory factor-1 (<i>NRF-1</i>) were investigated in a palmitate-induced C2C12 cell model of type 2 diabetes mellitus. The structures of these proteins were retrieved from the protein database, while bioactive compounds previously identified in <i>Solanum</i> spp. were obtained from PubChem site. Drug-likeness properties of these compounds (ligands) were assessed. The docked protein-ligand complexes were further analyzed using the Protein-Ligand Profiler web server. Our results showed that the studied compounds from <i>Solanum</i> spp. profoundly upregulated <i>GLUT4</i> expression (9-19-fold increase) in the C2C12 cell line, thus surpassing the effects of the standard anti-diabetic drug metformin. Additionally, activities of antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were elevated. Molecular docking showed that rutin, an abundant flavonoid from <i>Solanum</i> spp., had the highest binding affinity for the active sites of the target proteins. These findings provide new mechanistic insight into the anti-diabetic effects of <i>Solanum</i> spp., primarily due to its high rutin content, which plays a major role in the plant's glucose-regulating and antioxidant actions. Our findings underscore the potential use of <i>Solanum</i> spp. as an affordable functional food for managing type 2 diabetes, especially in developing countries with limited resources for purchasing drugs. Although promising, our findings should be further validated by clinical studies.