Abstract Diabetes mellitus is a chronic metabolic disease associated with progressive organ damage driven by hyperglycaemia-induced oxidative stress, inflammation, and cellular dysfunction. Cardiovascular complications remain a major cause of morbidity and mortality in diabetic patients. This study evaluated the antidiabetic, hepatoprotective, and pancreatic protective effects of a polyherbal formulation (PHF) comprising Curcuma longa, Nigella sativa, Prunus mahaleb, and Vitis vinifera in streptozotocin (STZ)-induced diabetic rats, integrating network pharmacology analysis with experimental validation. Network pharmacology analysis was performed to identify potential PHF-related targets and pathways associated with diabetes-related tissue injury. Rats were assigned to control, diabetic, metformin-treated, and PHF-treated (500 and 1000 mg/kg) groups. The 500 mg/kg dose was selected as an intermediate dose based on prior experimental studies reporting its biological relevance and safety in plant-derived formulations. Blood glucose, serum insulin, lipid profile, and pancreatic enzymes were measured. Hepatic and pancreatic tissues were examined using hematoxylin and eosin (H&E), Masson’s trichrome (MT), periodic acid–Schiff (PAS) staining, and immunohistochemistry for endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2–associated X protein (Bax), caspase-3, tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and vascular endothelial growth factor (VEGF). PHF treatment, particularly at 1000 mg/kg, normalised blood glucose ( p < 0.001), improved serum insulin, corrected dyslipidaemia, and restored amylase and lipase levels. Histological analysis demonstrated attenuation of steatosis, necrosis, fibrosis, and pancreatic β-cell loss. Immunohistochemical analysis showed reduced Bax and caspase-3 protein immunoreactivity and increased Bcl-2 and VEGF protein expression in PHF-treated groups. Network pharmacology analysis revealed 333 shared targets between PHF and diabetes-related injury, enriched in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), advanced glycation end product–receptor for AGE (AGE–RAGE), TNF, and metabolic signalling pathways. Hub genes including AKT1, IL6, TNF, STAT3, PTGS2, CASP3, and BCL2 showed reciprocal consistency between network pharmacology predictions and experimental immunohistochemical observations. To sum up, these findings support the potential of PHF as a multi-target therapeutic strategy against diabetes-induced hepatic and pancreatic injury.
Kıran et al. (2026) studied this question.