Evaluation of Natural Compounds from Cucurbita Pepo as Potential Inhibitors of Selected Proteins Linked With Glucose Metabolism

ABSTRACT The increasing prevalence of metabolic disorders such as diabetes mellitus necessitates the search for novel therapeutic agents with improved efficacy and safety profiles. In this study, we evaluated natural compounds from Cucurbita pepo as potential inhibitors of selected proteins linked with glucose metabolism, including Glycogen Synthase Kinase-Beta (GSKB), Sodium-glucose cotransporter 2 (SGLT2), and Dipeptidyl peptidase-4 (DPP4). Molecular docking studies were conducted using Schrodinger Maestro (v12.8) software to assess the binding affinity of the natural compounds with the target proteins. Our results revealed several natural compounds from Cucurbita pepo that exhibited promising binding affinity with the target proteins. Rutin emerged as the most promising inhibitor of GSKB, demonstrating the highest binding affinity with a GlideScore of -11.722 kcal/mol. Myricetin exhibited the highest binding affinity with SGLT2, while Rutin showed the highest binding affinity with DPP4. These findings suggest that natural compounds from Cucurbita pepo, particularly Rutin, Myricetin, and Quercetin, hold promise as potential inhibitors of proteins linked with glucose metabolism. Further validation through in vitro and in vivo studies is warranted to assess the therapeutic potential of these compounds for the management of metabolic disorders.