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The "Tianyu" Formulation Alleviates Rheumatoid Arthritis by Modulating the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis

Yueya Zhu1, Xinying Cai2, Qiuhan Zheng1

  • 1Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 25, 2026
PubMed
Summary
This summary is machine-generated.

The traditional Chinese medicine Tianyu formulation (TY) reduces pyroptosis and inflammation in rheumatoid arthritis by modulating the NLRP3 inflammasome pathway. This study investigated TY

Keywords:
NLRP3 inflammasomeRA‐HFLSTianyu formulationpyroptosisrheumatoid arthritis

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Area of Science:

  • Immunology and Inflammation Research
  • Traditional Chinese Medicine Pharmacology
  • Molecular Cell Biology

Background:

  • Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction.
  • Pyroptosis, a pro-inflammatory form of programmed cell death, plays a significant role in RA pathogenesis.
  • Targeting pyroptosis pathways, such as the NLRP3 inflammasome, presents a potential therapeutic strategy for RA.

Purpose of the Study:

  • To investigate the therapeutic effects of the Tianyu formulation (TY) on pyroptosis in rheumatoid arthritis.
  • To elucidate the underlying molecular mechanisms of TY in modulating pyroptosis in vitro and in vivo models of RA.
  • To identify key bioactive compounds in TY and their interactions with pyroptosis-related proteins.

Main Methods:

  • In vitro studies utilized tumor necrosis factor α (TNF-α)-induced human rheumatoid arthritis fibroblast-like synovial cells (RA-HFLS).
  • In vivo studies employed a collagen-induced arthritis (CIA) rat model.
  • Assays included cell viability, pyroptosis markers (LDH, IL-1β, IL-18), gene/protein expression analysis (RT-qPCR, Western blot, immunofluorescence), histopathology, and molecular docking simulations.

Main Results:

  • TY significantly inhibited RA-HFLS cell viability, proliferation, migration, and invasion, while reducing pyroptosis and inflammatory cytokine release.
  • TY downregulated key pyroptosis-related proteins in the NLRP3 inflammasome pathway (NLRP3, Caspase-1, GSDMD) in both in vitro and in vivo models.
  • TY treatment alleviated CIA symptoms, reduced joint swelling and inflammation, and improved joint pathology in rats. Molecular docking identified potent binding of TY's major compounds (e.g., Quercetin) to NLRP3, Caspase-1, and GSDMD.

Conclusions:

  • The Tianyu formulation effectively suppresses pyroptosis and alleviates joint inflammation in rheumatoid arthritis.
  • TY exerts its therapeutic effects by inhibiting the NLRP3/Caspase-1/GSDMD signaling pathway.
  • TY represents a promising therapeutic agent for rheumatoid arthritis, with its bioactive compounds potentially targeting key pyroptosis regulators.