A novel compound mixture mitigates hyperglycemia, insulin resistance, dyslipidemia, and oxidative stress in streptozotocin induced diabetic rats: A therapeutic drug lead for metabolic syndrome.

Plant-derived bioactive compounds play a crucial role in managing metabolic syndrome (MetS) components such as hyperglycemia, insulin resistance, and atherogenic dyslipidemia. The present study investigates the glucose and lipid lowering potential of a novel compound mixture composed of garcinol, piperine, butyl oleate, pipnoohine, and bismurrayanimbine (molar ratio of 9:33:1:4:1) and its effects on insulin resistance and atherogenic indices in streptozotocin induced (60 mgkg-1, ip) diabetic rats. The oral administration of the compound mixture at low (10 mgkg-1), therapeutic (25 mgkg-1), and high (50 mgkg-1) doses resulted in dose-dependent improvement in oral glucose tolerance with an increase of 6%, 9%, and 12%, respectively. There was a corresponding elevation in serum insulin (4%, 66%, 66%) and C-peptide (18%, 152%, 153%), along with reduction in serum fasting glucose (8%, 29%, 30%) and percentage of HbA1C (18%, 27%, 31%) compared to diabetic untreated rats (p < 0.05). Histopathological assessment of H and E-stained sections of the pancreatic tissue confirmed islet cell restoration. At the therapeutic dose, the mixture reduced homeostatic model assessment of insulin resistance (HOMA-IR) and increased homeostatic model assessment of β-cell functions (HOMA-β), aligning with pancreatic functions. Furthermore, all doses improved the antioxidant status and reversed atherogenic dyslipidemia in diabetic rats. Biochemical analysis revealed significant improvement in hepatic hexokinase activity at 25 and 50 mgkg-1 doses (p < 0.05). Overall, the compound mixture showed promising results as an adjunct therapy for managing hyperglycemia and atherogenic dyslipidemia associated with MetS, highlighting its potential to be developed as a therapeutic agent.