Annona muricata L. Leaf Methanolic Extract Modulates Glucose Homeostasis and Improves Pancreatic Hormones Protein Expression in Diabetic Rats

Type 2 diabetes mellitus represents an important worldwide health problem. Annona muricata L. (AM) is used for diabetes management. Additional research is required to elucidate its hypoglycemic mechanism; we evaluate its effect on serum leptin, glucagon, insulin, neuropeptide Y concentrations and protein levels of glucagon and insulin in diabetic model. Diabetes was induced in male Wistar rats using a high-fat diet (HFD) combined with 35 mg/kg streptozotocin (STZ). The animals were randomly assigned to four groups (n = 5): Ctrl (healthy animal), HFD (untreated HFD), AM (50 mg/kg of AM) and HFD Met (300 mg/kg of metformin). Treatments were administered orally for four weeks. Serum levels of leptin, glucagon, NPY, insulin, lipid renal and hepatic profiles were quantified before and after treatment. Pancreatic insulin and glucagon content were assessed by immunohistochemistry. Two-way ANOVA with repeated measures (intragroup) and ANOVA (intergroup) were used. The HFD AM group showed lower serum glucose (41.2%), total cholesterol (38.8%), triglycerides (69.6%) and NPY (73.4%) levels than pretreatment values (p < 0.05). Increased serum leptin concentration (53.7%), pancreatic insulin (42.0%), and glucagon (48.0%) protein levels (p < 0.05) were observed. Our study provides additional insights into the hypoglycemic effects of AM and supports its potential use as a complementary treatment for diabetes.