Icariin alleviates rheumatoid arthritis via regulating miR-223-3p/NLRP3 signalling axis

Area of Science:

• Immunology
• Molecular Biology
• Pharmacology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex pathogenesis and limited effective treatments.
• MicroRNAs (miRNAs), particularly miR-223-3p, are implicated in RA pathogenesis and may serve as biomarkers.
• Icariin has shown potential in alleviating RA in preclinical models, but its mechanism of action requires elucidation.

Purpose of the Study:

• To investigate the underlying mechanism of icariin's anti-rheumatoid arthritis effects.
• To explore the role of miR-223-3p and its interaction with NLRP3 in RA fibroblast-like synoviocytes (RA-FLS).
• To evaluate icariin's therapeutic potential for RA by targeting the miR-223-3p/NLRP3 signaling pathway.

Main Methods:

• Quantification of miR-223-3p expression in RA-FLS and RA patients using qRT-PCR.
• Assessment of RA-FLS cell proliferation (CCK-8, BrdU), apoptosis (flow cytometry, western blotting), and inflammatory cytokine secretion (ELISA).
• Confirmation of miR-223-3p and NLRP3 interaction using a dual luminescence-based reporter gene assay.

Main Results:

• Icariin inhibited RA-FLS proliferation and secretion of TNF-α, IL-1β, and IL-6, while promoting apoptosis.
• Icariin upregulated miR-223-3p expression in RA-FLS cells.
• MiR-223-3p directly targets the 3'-UTR of NLRP3, regulating its expression; inhibition of miR-223-3p reversed icariin's effects, and NLRP3 inhibition restored icariin's activity in miR-223-3p knockdown cells.

Conclusions:

• Icariin exerts anti-RA effects by inhibiting RA-FLS proliferation and inflammation while promoting apoptosis.
• The mechanism involves the regulation of the miR-223-3p/NLRP3 signaling pathway.
• Targeting the miR-223-3p/NLRP3 axis with icariin represents a potential therapeutic strategy for rheumatoid arthritis.