Abstract
Background Diabetic nephropathy (DN) is a major complication of type 2 diabetes mellitus, leading to end-stage renal disease. Berberis asiatica (BA) and Withania somnifera (WS) have demonstrated nephroprotective effects individually, but their combined potential remains unexplored. This study evaluates their individual and combined efficacy in improving renal function in streptozotocin-nicotinamide (STZ-NIC) induced diabetic rats. Methods A total of 78 adult Wistar rats were divided into 13 groups, including normal control (NC), diabetic control (DC), BA treated (250, 500, and 1,000 mg/kg), WS treated (250, 500, and 1,000 mg/kg), polyherbal combination (PHC) of BA and WS (250, 500, and 1,000 mg/kg), and standard drug-treated groups (metformin and glimepiride). Renal function markers (serum creatinine and urea) were measured, and histopathological analysis of kidney tissues was performed. Results Treatment with BA, WS, and PHC significantly reduced creatinine and urea levels compared to the DC group (p < 0.0001). The highest doses of BA (1,000 mg/kg) and WS (1,000 mg/kg) reduced creatinine by 14.5% and 15.8%, respectively, while PHC 1,000 mg/kg achieved a 21.1% reduction, comparable to standard drugs. Similarly, BA 1,000 mg/kg and WS 1,000 mg/kg reduced urea levels by 40.5% and 42.2%, respectively, whereas PHC 1,000 mg/kg exhibited the highest reduction of 55.9%, indicating a synergistic nephroprotective effect. Histopathological analysis confirmed reduced renal damage, with PHC 1,000 demonstrating nearly normal kidney architecture. The observed effects are attributed to the antioxidant, anti-inflammatory, and antihyperglycemic properties of BA and WS. Conclusion BA and WS at all doses showed significant nephroprotective effects. The combination of BA and WS (PHC 1,000) in equal amounts exhibited a synergistic effect, enhancing renal function and restoring kidney architecture in DN.