Objective: The present study aimed to evaluate the nephroprotective and antioxidant potential of aqueous extract of Simarouba glauca leaves in alloxan-induced diabetic rats through in vivo, in vitro, and biochemical assays.

Methods: Mature leaves of Simarouba glauca were collected, shade-dried, and powdered. Aqueous extract was prepared by boiling 10 g of the powder in 200 mL of water for 2 hours, followed by filtration and evaporation. In-vitro studies of Cellular assay such as MTT and malondialdehyde (MDA) were performed to evaluate cytotoxicity and lipid peroxidation. In addition, the antioxidant potential of the extract was assessed by Ferric Reducing Antioxidant Power, Phosphomolybdenum, DPPH radical scavenging, total antioxidant capacity, and nitric oxide assays to determine the IC₅₀ values of S. glauca. For in vivo studies, diabetes was induced in Wistar rats by intraperitoneal injection of alloxan monohydrate (150 mg/kg body weight). The animals were divided into five groups: Group I (normal control), Group II (diabetic control), Group III (standard drug Ramipril, 10 mg/kg), Group IV (diabetic rats treated with S. glauca extract, 250 mg/kg), and Group V (diabetic rats treated with S. glauca extract, 500 mg/kg). Fasting blood glucose was measured 72 hours post-induction. Urine and blood samples were collected weekly for four weeks to estimate urine creatinine, urine urea, urine albumin, serum creatinine, serum urea, and blood urea nitrogen (BUN). Serum calcium levels were analyzed at the end of the study, followed by histopathological examination of kidney tissues.

Results: Treatment with Simarouba glauca extract significantly reduced fasting blood glucose, improved renal function parameters, and preserved kidney histoarchitecture in diabetic rats. Antioxidant assays demonstrated strong radical scavenging and reducing activity. In vitro results confirmed the cytoprotective and antioxidant potential of the extract.