Triple Actions of a Novel Polyherbal JDED Formulation Restores Glycemic and Reproductive Function in Diabetic Male Rats Via Antioxidant, Hormonal and Metabolomic Modulation

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and often leads to metabolic and reproductive complications. Current treatments have limitations, including side effects and limited efficacy, prompting interest in safer, multi-targeted alternatives. This study evaluated the antioxidant activity, phytochemical profile, and therapeutic effects of JDED in streptozotocin-induced diabetic male rats. Antioxidant capacity was assessed using DPPH and FRAP assays, with total phenolic (TPC) and flavonoid content (TFC) quantified. In vivo assessments included fasting blood glucose (FBG), antioxidant enzymes, reproductive hormones, semen quality, organ weights, and histopathology of the pancreas and testis. FTIR spectroscopy profiled functional groups, while UHPLC-ESI-MS/MS identified bioactive metabolites and metabolic pathway enrichment analysis was done to predict the pathways involved. JDED showed strong antioxidant activity (TPC: 134.27±0.02 mg GAE/100g; TFC: 42.06±0.35 mg GAE/100g; DPPH: 97.39±1.04 µg/mL; FRAP: 4.58±0.00 mM Fe²⁺/g). Treatment with JDED and metformin significantly reduced FBG and increased SOD (1.77-fold) and CAT (6.5-fold). FSH and LH levels rose by 1.74- and 1.75-fold, with a slight increase in testosterone. Sperm motility and count improved by 3.9- and 2.6-fold, while abnormal morphology decreased twofold. Relative weights of the testis and pancreas improved, and histology showed tissue restoration. FTIR spectroscopy identified functional groups, and UHPLC-ESI-MS/MS revealed 53 bioactive metabolites. Pathway enrichment indicated modulation of steroid biosynthesis, fatty acid degradation, TCA cycle, and carbohydrate metabolism. These findings suggest JDED exerts multi-targeted effects through antioxidant, hormonal, and metabolic regulation, supporting its potential as a natural therapeutic agent for diabetes-related complications.