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International Urology and Nephrology

23-04-2024 | Diabetic Nephropathy | Nephrology - Original Paper

Astragalus polysaccharide attenuates diabetic nephropathy by reducing apoptosis and enhancing autophagy through activation of Sirt1/FoxO1 pathway

Authors: Yanmei Xu, Chen Xu, Jie Huang, Chuanwen Xu, Yan Xiong

Published in: International Urology and Nephrology

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Abstract

Objective

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetic patients. Astragalus polysaccharide (APS) is a natural active ingredient in Astragalus membranaceus with anti-hypertensive and anti-oxidative properties. This study aimed to explore the protective roles of APS and its underlying mechanisms in DN.

Methods

After the establishment of a rat model of DN by a high-fat diet and treatment with 30 mg/kg streptozotocin (STZ), the effects of 100 mg/kg APS on the levels of serum creatinine, blood urea nitrogen, blood glucose, and urinary albumin-to-creatinine ratio were measured. Histopathological alterations in renal tissues, renal cell apoptosis, renal inflammation, and oxidative stress were examined. The impacts of 0–200 μg/mL APS on the viability and apoptosis in high glucose (HG)-stimulated podocytes were measured by Cell Counting Kit-8 assays and flow cytometry, respectively. The expression of genes was tested by immunoblotting, quantitative real-time PCR, and immunofluorescence staining.

Results

APS enhanced the expression of podocin and nephrin, increased viability, and reduced apoptosis in HG-induced podocytes. APS treatment abrogated high glucose-mediate suppression of autophagy in podocytes by activating the Sirt1/FoxO1 pathway. The Sirt1 inhibitor EX-527 eliminated the ameliorative effects of APS on renal dysfunction and renal tissue damage, as well as the inhibitory effects of APS on oxidative stress, inflammation, and apoptosis in DN rats. Moreover, EX-527 inhibited APS-induced autophagy activation in DN rats.

Conclusion

APS mitigated DN under hyperglycemic conditions by activating the Sirt1/FoxO1 autophagy pathway, suggesting that APS is a promising agent for DN treatment.
Appendix
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Metadata
Title
Astragalus polysaccharide attenuates diabetic nephropathy by reducing apoptosis and enhancing autophagy through activation of Sirt1/FoxO1 pathway
Authors
Yanmei Xu
Chen Xu
Jie Huang
Chuanwen Xu
Yan Xiong
Publication date
23-04-2024
Publisher
Springer Netherlands
Published in
International Urology and Nephrology
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-024-04038-0
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