Development and evaluation of a polyherbal formulation for dyslipidemia associated with type 2 diabetes

To systematically evaluate a polyherbal formulation (PHF) comprising Gymnema sylvestre, Terminalia arjuna, Curcuma longa, and Trigonella foenum-graecum for its antidiabetic and anti-dyslipidemic potential through integrated in-vitro mechanistic studies and in-vivo efficacy and safety evaluations. The optimized PHF underwent phytochemical screening and UHPLC-HRMS metabolomic profiling. In-vitro antioxidant activity was assessed via DPPH and ABTS assays, while enzyme inhibition assays evaluated effects on ?-amylase, ?-glucosidase, HMG-CoA reductase, and pancreatic lipase. In-vivo efficacy was tested in high-fat diet/streptozotocin-induced diabetic Wistar rats (n=6/group) treated with PHF (100, 200, 400 mg/kg) or metformin (50 mg/kg) for 28 days. Glycemic parameters, lipid profiles, hepatic/renal function markers, oxidative stress markers (SOD, MDA) and inflammatory cytokine (TNF-?) were measured. Histopathological examination of pancreas, liver, and kidney was performed. Acute and sub-chronic toxicity studies established safety profile. Phytochemical screening revealed abundant presence of alkaloids, flavonoids, tannins, and phenolics. UHPLC-HRMS confirmed marker compounds including gymnemic acid, arjunic acid, curcumin, and trigonelline. PHF demonstrated potent antioxidant activity (DPPH IC50 : 42.67 µg/mL; ABTS IC50 : 38.94 µg/mL) and significant enzyme inhibition (?-amylase IC50 : 45.32 µg/mL; ?-glucosidase IC50 : 38.76 µg/mL; HMG-CoA reductase IC50 : 52.18 µg/mL; pancreatic lipase IC50 : 68.43 µg/mL). In diabetic rats, PHF (400 mg/kg) reduced fasting blood glucose by 49.1% (p<0.01) and HbA1c from 9.87% to 5.97%, comparable to metformin. Lipid profile improved significantly with 34.0% reduction in total cholesterol, 40.3% reduction in triglycerides, 47.1% reduction in LDL-C and 55.7% increase in HDL-C (p<0.01). PHF restored SOD activity (84.7% of normal), reduced MDA by 61.4% and TNF-? by 58.9% (p<0.01). Histopathology confirmed preservation of pancreatic islet architecture, reduced hepatic steatosis, and protection against renal damage. Toxicity studies demonstrated safety up to 2000 mg/kg. In conclusion, the polyherbal formulation exhibits significant antidiabetic and anti-dyslipidemic effects through multi-target mechanisms including enzyme inhibition, antioxidant activity and organ protection. The favorable safety profile and comprehensive metabolic benefits position this formulation as a promising candidate for clinical evaluation in managing diabetic dyslipidemia.