Year: 2026
Type: article
Abstract: Introduction: Although dioscin, a natural steroidal saponin, has demonstrated renal protective effects, its mechanism related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in diabetic kidney disease (DKD) remains incompletely characterized. Methods: A DKD rat model was established and treated with dioscin. Metabolic parameters (blood glucose, urine protein, serum creatinine, renal index) were measured. Renal histopathology was evaluated via Hematoxylin-Eosin (H&E), Periodic Acid-Schiff (PAS) staining, and transmission electron microscopy. Immunohistochemistry and immunofluorescence were used to assess Nrf2/HO-1, and reactive oxygen species (ROS) levels. In vitro, high glucose (HG)-induced HK-2 cells were subjected to Nrf2 knockdown and treated with dioscin. Cell viability and ROS levels were examined. Results: Dioscin administration significantly reduced fasting blood glucose by 60%, glucose tolerance by 40%, insulin levels by 50%, urinary protein by 50%, and serum creatinine levels by 35% in DKD rats (p<0.001), while ameliorating histopathological damage including mesangial hyperplasia, and mitochondrial disruption (p<0.001). Moreover, dioscin upregulated Nrf2 and HO-1 by 50% (p<0.01) and 30% (p<0.05), respectively, and reduced renal ROS levels by 55% (p<0.001). In HG-stimulated HK-2 cells, dioscin increased cell viability from 55% to 70% (p<0.001), and reduced ROS generation by 90% (p<0.001) as well as mitochondrial ROS accumulation by 50% (p<0.001). However, Nrf2 knockdown reversed these protective effects. Conclusion: Dioscin attenuates renal injury and oxidative stress in DKD by activating the Nrf2/HO-1 signaling pathway, underscoring its potential as a novel therapeutic agent for DKD.
DOI: 10.2147/dmso.s590914
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,836
OpenAlex ID: W7224086036