Anti-hyperglycemic and protective effects of honey, bee pollen, and propolis in acute and chronic hyperglycemia: in vivo and in silico evidence

Diabetes mellitus is a major global health challenge associated with high morbidity and mortality. Natural products, including bee-derived products, are valued for their bioactive compounds with potential antidiabetic properties. The present study aimed to experimentally evaluate and compare the antihyperglycemic and protective effects of honey, propolis, bee pollen, and their combination on acute and chronic hyperglycemia. Acute hyperglycemia was assessed using the oral glucose tolerance test (OGTT), while chronic hyperglycemia was evaluated using a streptozotocin (STZ)-induced experimental type 1 diabetic model. Diabetic animals were orally treated for three weeks with distilled water (10 mL/kg), glibenclamide (2.5 mg/kg), honey (1 g/kg), bee pollen (100 mg/kg), propolis (100 mg/kg), or their mixture (10 mL/kg, 1:1:1, v/v/v). Glycémia, body weight, biochemical (AST, ALT, urea, creatinine), inflammatory (IL-6, CRP), and histological parameters were evaluated. In addition, molecular docking was performed to explore potential interactions between major phenolic compounds and key metabolic (α-amylase, α-glucosidase) and inflammatory targets (DPP-IV and COX-2). In the OGTT, all bee products significantly reduced postprandial glucose excursions, with honey showing the most pronounced effect. In STZ-induced diabetic rats, bee products markedly reduced blood glucose levels, prevented body weight loss, improved hepatorenal biomarkers, decreased IL-6 and CRP levels, and preserved pancreatic histological features, with the mixture showing the most sustained overall improvement. Docking analyses revealed favorable predicted interactions between selected phenolic compounds and α-amylase, α-glucosidase, DPP-IV, and COX-2. These findings provide experimental support for the traditional use of bee-derived products in the management of hyperglycemia and diabetes-associated inflammatory and tissue alterations.