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 E 2 (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.
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