Protective effects of Morus alba Linn leaf extract on streptozotocin-induced diabetic nephropathy in mice model

• Morus alba Linn leaf extract (MAE) showed anti-diabetic and renoprotective effects in diabetic nephropathy mouse model. • MAE significantly lowered blood glucose and improved serum lipid profiles. • MAE improved renal function markers and partially reversed diabetes-induced renal structural changes. • MAE showed comparable efficacy to dapagliflozin in managing diabetic nephropathy. Diabetic nephropathy, a major microvascular complication of type 2 diabetes, arises from chronic hyperglycemia-induced renal dysfunction. Current therapies have limited efficacy in halting its progression. The aim of this study was to evaluate the nephroprotective potential of Morus alba Linn leaf extract (MAE) against streptozotocin-induced diabetic nephropathy in a mouse model. Diabetic nephropathy was induced in Swiss mice using multiple low-dose streptozotocin intraperitoneal injections. Mice received MAE (820.8 or 2462.4 mg/kg) or dapagliflozin (1 mg/kg) orally for 28 days. Morus alba Linn leaf extract reduced fasting blood glucose (FBG), triglycerides, total cholesterol, lipoprotein combine index (LCI), and urinary albumin-creatinine ratio (UACR) while increasing creatinine clearance (Ccr) compared to diabetic controls. Specifically, after 28 days of treatment, MAE at 820.8 mg/kg reduced FBG from 16.56 ± 3.90 mmol/L in diabetic controls to 9.69 ± 2.15 mmol/L (p < 0.01), and at 2462.4 mg/kg to 12.51 ± 4.17 mmol/L (p < 0.05). Additionally, Ccr increased from 16.80 ± 10.80 µl/min in diabetic controls to 41.84 ± 27.02 µl/min with low-dose MAE (p < 0.05) and 39.72 ± 15.54 µl/min with high-dose MAE (p < 0.01). Histopathological analysis revealed reduced glomerulosclerosis, tubular degeneration, and pancreatic islet damage in MAE-treated groups. However, MAE did not improve glucose tolerance in the oral glucose tolerance test, and changes in renal malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) were not significant, suggesting limited effects on dynamic glucose handling and oxidative/inflammatory pathways. A trend toward increased glutathione (GSH) was observed. These findings suggest MAE as a promising candidate for managing diabetic nephropathy, but further mechanistic and clinical studies are needed to validate its therapeutic potential.