Rhein attenuates obesity-related glomerulopathy by inhibiting the P2X7R/NLRP3 inflammasome pathway and protecting podocytes

Document Type : Original Article

Authors

1 Department of Nephrology, The Third People’s Hospital Affiliated to Fujian Univer-sity of Traditional Chinese Medicine, Fuzhou, Fujian, China

2 State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Bio-medicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecu-lar Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, China

3 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, China

4 Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, Fujian, China

5 Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China

6 The Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China

10.22038/ijbms.2025.88054.19020

Abstract

Objective(s): To investigate the renoprotective effects of Rhein in obesity-related glomerulopathy (ORG) by inhibiting the P2X7 receptor (P2X7R)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway.
Materials and Methods: ORG was induced in C57BL/6J mice with a high-fat diet (HFD) for 10 weeks, fol-lowed by oral Rhein treatment (70 or 300 mg/kg/day) for 10 weeks. Renal function, histology, and podocyte injury were assessed. In vitro, leptin-induced podocyte injury was treated with Rhein or P2X7R antagonists (KN-62 or A-438079). P2X7R/NLRP3 activation, inflammation, and oxidative stress were evaluated.
Results: HFD-induced weight gain, dyslipidemia, renal dysfunction, glomerular hypertrophy, and podocyte injury. Rhein reduced serum triglycerides (TG) and total cholesterol (TC), lowered blood urea nitrogen (BUN), improved urinary protein excretion, and alleviated histological damage. Rhein inhibited P2X7R and NLRP3 activation, down-regulated caspase-1, interleukin (IL)-1β, and IL-18, and restored podocyte markers (Nephrin, Podocin). In vitro, Rhein mitigated leptin-induced podocyte injury and inflammasome activation.
Conclusion: Rhein protects against ORG by suppressing the P2X7R/NLRP3 pathway, reducing inflammation and oxidative stress, and preserving podocyte integrity, highlighting its therapeutic potential.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 12
December 2025
Pages 1743-1748

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