Abstract

Diabetic nephropathy (DN), a severe microvascular complication of diabetes mellitus, is a leading cause of end-stage renal disease. Current therapies that focus on glycemic and blood pressure control are insufficient, prompting the need for novel interventions. While the systemic metabolic effects of ethanolic extract of Strychnos potatorum seeds (EESP), including changes in body weight, blood glucose, and insulin levels, and its role in upregulation of fibroblast-specific protein-1, have been previously reported, this study investigated the renoprotective potential of the EESP in a streptozotocin-induced rat model of DN. The study focused on the modulation of the tight junction protein Zonula occludens-1 (ZO-1), which maintains the integrity of the glomerular filtration barrier. Thirty male Wistar albino rats were divided into five groups and treated with EESP (500 mg/kg) or metformin (50 mg/kg) for 30 days. Urine analysis, renal histopathology, electron microscopy study, ZO-1 immunohistochemistry, gene expression, and protein expression were analyzed. EESP administration significantly improved renal function by reducing the urinary albumin (p = 0.03), protein (p = 0.01), urea, and creatinine levels. It alleviated oxidative stress markers such as lipid peroxidation, hydrogen peroxide, and protein carbonyls, while restoring antioxidant enzyme (glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase) activity (p = 0.001). Histological and ultrastructural analyses revealed reduced glomerular basement membrane thickening, tubular atrophy, and podocyte damage. Notably, EESP upregulated ZO-1 expression at both the gene (2.25-fold) and protein (3.6-fold) levels, suggesting improved slit diaphragm integrity and reduced proteinuria. These findings suggest that EESP offers a multifaceted renoprotective effect in DN through the mitigation of oxidative stress, structural preservation, and enhancement of ZO-1 expression. Further mechanistic and clinical studies are warranted to validate S. potatorum as a potential therapeutic candidate for DN.

Key words: Strychnos potatorum, Zonula Occludens – 1, Oxidative stress, Streptozotocin, Glomerular filtration barrier