Dioscin Alleviates Diabetic Kidney Disease via Activation of the Nrf2/HO-1 Signaling Axis.
- 1Department of Nephrology, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, People's Republic of China.
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.
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BibTeX
@article{li2026dioscin,
title = {{Dioscin Alleviates Diabetic Kidney Disease via Activation of the Nrf2/HO-1 Signaling Axis.}},
author = {Yan Li and Xiaoyun Zhang and Mansheng Zhang and Subo Li and Yubo Chen and Li Zhang},
journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
year = {2026},
month = oct,
doi = {10.2147/dmso.s590914},
url = {https://europepmc.org/article/MED/42968987},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Dioscin Alleviates Diabetic Kidney Disease via Activation of the Nrf2/HO-1 Signaling Axis.
AU - Yan Li
AU - Xiaoyun Zhang
AU - Mansheng Zhang
AU - Subo Li
AU - Yubo Chen
AU - Li Zhang
PY - 2026
DA - 2026/10/28
JO - Diabetes, metabolic syndrome and obesity : targets and therapy
DO - 10.2147/dmso.s590914
UR - https://europepmc.org/article/MED/42968987
AB - 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.
SN - 1178-7007
ER -