Liquiritigenin Ameliorates Rheumatoid Arthritis by Modulating the Nrf2/NF-κB/NLRP3 Pathway in Fibroblast-like...

Area of Science:

• Immunology
• Pharmacology
• Biochemistry

Background:

• Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint destruction and synovial inflammation.
• Aberrant activation of fibroblast-like synoviocytes (FLSs) is a key pathological mechanism in RA.
• Liquiritigenin (LIQ), a flavonoid from licorice root, has known anti-inflammatory and antioxidant properties, but its role in RA is unexplored.

Purpose of the Study:

• To investigate the anti-rheumatoid arthritis (RA) effects of Liquiritigenin (LIQ).
• To elucidate the mechanisms by which LIQ acts on fibroblast-like synoviocytes (FLSs) in RA.
• To determine LIQ's impact on the Nrf2/NF-κB/NLRP3 signaling pathway in RA models.

Main Methods:

• Utilized a Complete Freund's adjuvant (CFA)-induced rat model and a TNF-α-stimulated MH7A cell model for RA.
• Assessed LIQ's effects on RA manifestations, joint damage, FLS activation, oxidative stress, and inflammation in vivo and in vitro.
• Validated LIQ's modulation of the Nrf2/NF-κB/NLRP3 pathway using immunofluorescence and Western blotting.

Main Results:

• LIQ significantly reduced joint swelling, bone damage, and synovial inflammation in CFA-induced rats.
• LIQ inhibited proliferation, migration, and invasion of TNF-α-stimulated MH7A cells, decreasing reactive oxygen species (ROS), IL-1β, and IL-18 levels.
• LIQ activated Nrf2 while inhibiting NF-κB and NLRP3, thereby reducing inflammation and oxidative stress. Nrf2 inhibition partially reversed these effects.

Conclusions:

• Liquiritigenin (LIQ) demonstrates significant anti-RA effects by suppressing FLS inflammation and aberrant activation.
• LIQ's therapeutic mechanism in RA involves the modulation of the Nrf2/NF-κB/NLRP3 signaling pathway.
• LIQ presents a promising therapeutic candidate for rheumatoid arthritis treatment.