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

Lifang Wei1, Jinwen Zhang2, Liangding Dou2

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

Abstract

Insights

Rhein, a natural compound, shows renoprotective effects against obesity-related glomerulopathy by inhibiting the P2X7 receptor (P2X7R)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway, reducing inflammation and preserving kidney function.

Area of Science:

  • Nephrology
  • Pharmacology
  • Immunology

Background:

  • Obesity-related glomerulopathy (ORG) is a growing concern linked to metabolic dysfunction.
  • The P2X7 receptor (P2X7R)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway is implicated in kidney injury.

Purpose of the Study:

  • To investigate the renoprotective effects of Rhein in ORG.
  • To determine if Rhein inhibits the P2X7R/NLRP3 inflammasome pathway.

Main Methods:

  • Obesity-related glomerulopathy was induced in mice using a high-fat diet (HFD).
  • Mice were treated with Rhein (70 or 300 mg/kg/day) or P2X7R antagonists.
  • Renal function, histology, podocyte injury, inflammasome activation, inflammation, and oxidative stress were assessed.

Main Results:

  • Rhein treatment reduced weight gain, dyslipidemia, renal dysfunction, and histological damage in HFD-induced ORG mice.
  • Rhein inhibited P2X7R and NLRP3 inflammasome activation, decreasing inflammatory markers (caspase-1, IL-1β, IL-18).
  • Rhein mitigated leptin-induced podocyte injury and inflammasome activation in vitro.

Conclusions:

  • Rhein demonstrates significant renoprotective effects against obesity-related glomerulopathy.
  • Rhein's mechanism involves suppressing the P2X7R/NLRP3 inflammasome pathway, reducing inflammation and oxidative stress.
  • Rhein holds therapeutic potential for managing ORG.

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