Abstract
Diabetes mellitus often requires long-term therapy that can cause side effects, prompting interest in alternative approaches. Pumpkin seeds, traditionally used for their antidiabetic effects, are often combined with conventional drugs, raising concerns about potential interactions. The present study aimed to evaluate the possible interaction of ethanolic extract of pumpkin seeds with glibenclamide in streptozotocin-induced diabetic rats, supported by in-silico analysis. In-silico studies, including network pharmacology, gene ontology, and molecular docking, were performed to predict the multitargeting potential of pumpkin seed phytoconstituents against diabetes-related targets. Albino Wistar rats were injected with streptozotocin (45 mg/kg, i.p.) to induce diabetes and treated for 28 days with ethanolic extract of pumpkin seeds (200 mg/kg), glibenclamide (5 mg/kg), and their combination. Blood glucose levels and body weight were monitored periodically. At the end of the treatment, oral glucose tolerance, lipid profile, glycated hemoglobin, insulin, renal biomarkers, and histopathology of pancreas, liver, and kidney were assessed. In-silico analysis identified PIK3R1, STAT3, MAPK1, and ESR1 as key diabetes-related targets of pumpkin seed phytoconstituents, highlighting their multitargeting potential. Oral administration of ethanolic extract of pumpkin seeds, glibenclamide, and their combination significantly improved body weight, lowered blood glucose levels, enhanced glucose tolerance, and restored lipid and renal profiles, with combination therapy showing more pronounced effects. Histology confirmed preservation of pancreatic, hepatic, and renal integrity. Co-administration of ethanolic extract of pumpkin seeds and glibenclamide exerts synergistic antidiabetic effects, indicating its potential as an effective adjunct to conventional therapy for managing diabetes and its associated complications.