Integration of in vivo and network pharmacology analysis reveals the anti-diabetic mechanisms of Phyllanthus emblica ethyl acetate extract

Present study integrates the ethyl acetate fraction of Phyllanthus emblica (PE; Amla) with network pharmacology and bioinformatics analyses focused on adipokine-related targets to generate predictive insights into its potential metabolic and antidiabetic mechanisms. The phytoconstituents of PE extract were analyzed by gas chromatography mass spectrometry (GC-MS). Rats with diabetes caused by streptozotocin (STZ) were given low, medium, and high dosages of PE extract; metformin was used as a positive control. The physiological and biochemical parameters, such as fasting blood glucose (FBG), total cholesterol, triglycerides, adiponectin, and leptin, were assessed. The architecture of pancreatic islet was examined histologically. The network pharmacology was used to identify bioactive compounds, construct drug-disease and protein-protein interaction networks, and perform pathway enrichment analysis. The PE extract exhibited significant, dose-dependent anti-diabetic activity. The high dose (400 mg/kg) produced effects comparable to metformin, significantly lowering FBG, total cholesterol, triglycerides, and leptin levels. Histopathology revealed pancreatic islet protection. The network analysis identified six key polyphenols: gallic acid, pyrogallol, quercetin, ellagic acid, ascorbic acid, and epigallocatechin gallate. The core molecular targets included AKT1, IRS1, PPARG, and MAPK8. The extract’s activity is mediated through a synergistic, multi-target mechanism involving β -cell protection, glucose-lowering, and lipid modulation. The integration of in vivo and computational analyses validates the therapeutic potential of PE for diabetes management. The findings support its role as a promising multi-target natural treatment and establish a basis for future translational research.