Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast – like synoviocytes of collagen induced arthritic rats

Abstract.

Objective:

To investigate the effects of Paeoniflorin (Pae) on inflammatory mediators and G protein – coupled signaling in fibroblast – like synoviocytes (FLS) from collagen induced arthritic (CIA) rats.

Methods:

SD rats were injected with type II collagen. Pae (25, 50, 100 mg· kg⁻¹) was administered to CIA rats. The inflammation of CIA rats was evaluated by paw swelling, arthritis index and histopathology of joints. FLS were isolated and cultured. Interleukin (IL)-1 activity was measured by the ³H-TdR – intake method Tumor necrosis factor alpha (TNF-alpha), prostaglandin E₂ (PGE₂) and cAMP were measured by radioimmunoassay. Protein kinase A (PKA) was assessed by luminescent kinase assay. Gi was detected by Western blot.

Results:

Inflammation in CIA rats was accompanied by hyperplastic synovium, pannus and cartilage erosion in joints. IL-1 activity and Gi expression increased, PGE₂ and TNF-alpha production were enhanced, but cAMP level and PKA activity decreased. Pae significantly suppressed the inflammatory response and inflammatory mediators (IL-1, TNF-alpha and PGE₂) in vivo. Pae inhibited Gi expression and restored cAMP level and PKA activity in FLS of CIA rats in vivo and vitro.

Conclusion:

Inflammatory mediators and G protein - coupled signaling were associated with the pathogenesis of synovitis in CIA rats. Pae, as a new monomer, had anti-inflammatory effects on the animal model of CIA in rats, but also had regulatory effects on FLS from CIA rats in vitro. These results highlight Pae as a good candidate for therapeutic intervention in RA.