Acetone Extract of Annona Muricata Linn Leaf Counteracts Hyperglycemia-Associated Metabolic Dysregulation by Modulating Oxidative Stress and Hepatic Carbohydrate Metabolism in Streptozotocin-Induced Diabetic Rats

Annona muricata is widely recognized for its rich phenolic composition and potent antioxidant activity, suggesting therapeutic potential in diabetes management. This study investigated the mechanistic antidiabetic effects of acetone extract of A. muricata leaf on hepatic carbohydrate metabolism, oxidative stress, and hepatic function in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in forty-two male Wistar rats by intraperitoneal injection of STZ (55 mg/kg). Diabetic animals (n = 7 per group) were treated with 25, 50, and 100 mg/kg of the extract (yield: 10.08% w/w) for 28 days, while metformin (200 mg/kg) served as the standard drug. Hepatic antioxidant enzyme activities, lipid peroxidation, serum albumin, lactate dehydrogenase (LDH), and histopathological alterations were evaluated to assess oxidative status and hepatic function, alongside the activities of key carbohydrate-metabolizing enzymes and mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter 4 (GLUT4). Administration of the acetone extract significantly enhanced hepatic antioxidant defenses, as demonstrated by increased levels of glutathione and increased activities of antioxidant enzymes, accompanied by a marked reduction in lipid peroxidation. Additionally, the extract significantly restored serum albumin levels and reduced LDH activity, indicating improved hepatocellular integrity. Furthermore, the extract significantly impacted the activities of carbohydrate-metabolizing enzymes and restored the expression of PPAR-γ and GLUT4 toward physiological levels. These results suggest that the antidiabetic activity of A. muricata may be mediated by the attenuation of oxidative stress, preservation of hepatic function, and regulation of hepatic carbohydrate metabolism and glucose transporter signalling pathways, highlighting its potential as a promising phytotherapeutic agent for the management of diabetes.