Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid...

Area of Science:

• Immunology
• Pharmacology
• Traditional Chinese Medicine

Background:

• Rheumatoid arthritis (RA) is characterized by inflammation and joint destruction.
• Fibroblast-like synoviocytes (RA-FLS) play a crucial role in RA pathogenesis.
• Understanding the molecular mechanisms of RA-FLS is vital for developing new therapies.

Purpose of the Study:

• To investigate the effects of Shentong Zhuyu Decoction on RA-FLS.
• To elucidate the underlying molecular mechanisms, including cell proliferation, migration, invasion, and apoptosis.
• To explore the involvement of the MAPK p38/PPARγ/CTGF pathway.

Main Methods:

• Established a collagen-induced arthritis (CIA) rat model.
• Isolated and identified RA-FLS.
• Assessed RA-FLS viability, apoptosis, cell cycle, migration, and invasion using CCK-8, flow cytometry, wound-healing, and Transwell assays.
• Quantified gene and protein expression of key molecules (MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, cyclin D1) via qRT-PCR and Western blotting.

Main Results:

• Shentong Zhuyu Decoction significantly reduced RA-FLS viability, migration, invasion, and IL-1β/MMP-3 secretion.
• The decoction increased RA-FLS apoptosis and inhibited G1 to S phase transition.
• Expression of Bcl-2, CDK4, cyclin D1, p-MAPK p38, and CTGF was decreased, while Bax, caspase-3, and PPARγ levels were increased.
• Effects mirrored those of MAPK P38 inhibitor and PPARγ agonist.

Conclusions:

• Shentong Zhuyu Decoction effectively inhibits RA-FLS proliferation, inflammatory response, migration, and invasion.
• The decoction promotes RA-FLS apoptosis and cell cycle arrest.
• The therapeutic effects are mediated through the MAPK p38/PPARγ/CTGF signaling pathway.