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

## TL;DR

Rhein helps protect the kidneys in obesity-related glomerulopathy by reducing inflammation and preserving podocyte function.

## Contribution

This study demonstrates that Rhein attenuates ORG by inhibiting the P2X7R/NLRP3 inflammasome pathway and protecting podocytes.

## Key findings

- Rhein reduced serum triglycerides, cholesterol, and blood urea nitrogen in HFD-induced ORG.
- Rhein inhibited P2X7R/NLRP3 activation and downregulated inflammatory markers like IL-1β and IL-18.
- Rhein preserved podocyte markers and mitigated leptin-induced podocyte injury in vitro.

## Abstract

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.

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.

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.

Rhein protects against ORG by suppressing the P2X7R/NLRP3 pathway, reducing inflammation and oxidative stress, and preserving podocyte integrity, highlighting its therapeutic potential.