Standardized chamuangone extract from Garcinia cowa leaves ameliorates hyperglycemia and metabolic dysfunction through multi-target mechanisms in nicotinamide–streptozotocin-induced diabetic rats

Garcinia cowa Roxb. a Southeast Asian edible medicinal plant, has traditionally been used to manage diabetes mellitus (DM). Its leaves are rich in chamuangone, a major bioactive polyprenylated benzophenone. Thereby, this study aimed to develop standardized chamuangone-enriched extract (CEE) from its leaves for antidiabetic evaluation. CEE was prepared by microwave-assisted extraction (MAE), along with column chromatography, and standardized via HPLC analysis. The antihyperglycemic and antihyperlipidemic assessment of CEE was conducted through computational, in vitro enzyme (α–glucosidase and pancreatic lipase) inhibitory, and in vivo assays using nicotinamide–streptozotocin (NA–STZ)-induced male diabetic rats. Experimentally, the diabetic rats were divided into five groups ( n = 6). Group I was given vehicle; group II received repaglinide (1 mg/kg); and groups III, IV, and V were orally administered with CEE at 25, 50, and 100 mg/kg, respectively, for 28 days. CEE, containing 67.0 ± 2.0% w/w of chamuangone, demonstrated strong docking scores against α-glucosidase (−8.0 kcal/mol) and pancreatic lipase (−8.5 kcal/mol), corroborating in-vitro enzyme inhibitory activities (IC 50 = 3.41 and 11.14 µg/mL, respectively). Molecular dynamics (MD) simulations revealed stable complexation of chamuangone with α-glucosidase (RMSD: 0.19 nm and RMSF: 0.10 nm), unlike pancreatic lipase (RMSD: 0.33 nm and RMSF: 0.18 nm). Finally, CEE (25, 50, and 100 mg/kg) ameliorated insulin, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), food/water intake, body mass index, cholesterol, triglycerides, high/low density lipoproteins, aspartate aminotransferase, alanine aminotransferase, creatinine, and blood urea nitrogen levels in diabetic rats. Overall, this study highlights the promising potential of CEE in the management of DM.