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Paeoniflorin inhibits function of synoviocytes pretreated by rIL-1α and regulates EP₄ receptor expression
- Chang, Yan, Zhang, Lei, Wang, Chun, Jia, Xiao-Yi, Wei, Wei
- Journal of ethnopharmacology 2011 v.137 no.3 pp. 1275-1282
- Paeonia lactiflora, Western blotting, adjuvants, anti-inflammatory activity, arthritis, chickens, collagen, cyclic AMP, glucosides, immune response, interleukin-1, protein synthesis, rats, receptors, roots, tumor necrosis factors
- ETHNOPHARMACOLOGICAL RELEVANCE: To investigate the effect of the Paeoniflorin (Pae), a main active component of total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora, on regulation of synoviocytes cultured from rats collagen-induced arthritis (CIA) in vitro. MATERIALS AND METHODS: CIA was induced in male Sprague-Dawley rats immunized with chicken type II collagen (CCII) in Freund's complete adjuvant. The levels of interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), prostaglandin E₂ (PGE₂) and cyclic adenosine monophosphate (cAMP) were measured by radioimmunoassay. The proliferation responses was determined by the 3-(4,5-2dimethylthiazal-2yl) 2,5-diphenyltetrazoliumbromide (MTT) assay. Expression of E-prostanoid (EP₄) receptor was detected by Western blotting technique. RESULTS: Treatment of Pae (2.5, 12.5, 62.5μg/ml) significantly decreased the production of IL-1 and TNF-α. Recombinant interleukin-1 (rIL-1α) (10ng/ml) apparently stimulated synoviocyte, thymocyte and splenocyte proliferation, and Pae (12.5, 62.5μg/ml) inhibited abnormal proliferation responses stimulated by rIL-1α. Moreover, rIL-1α time- and concentration-dependently increased production of PGE₂. The production of PGE₂ produced by synoviocytes from CIA rats significantly inhibited by administration of Pae (12.5, 62.5μg/ml). rIL-1α (10ng/ml) decreased cAMP of synoviocytes cells treated for 24h. Similarly rIL-1α (0.1, 1, 10ng/ml) induced a concentration-dependent decrease in the production of cAMP at 24h. Pae (12.5, 62.5μg/ml) increased the production of cAMP in synoviocytes. The immunoblot, Pae (12.5, 62.5μg/ml) apparently increased the expression of EP₄ receptor in synoviocytes stimulated by rIL-1α (10ng/ml). CONCLUSIONS: The present study indicates that Pae might exert its anti-inflammatory effects through suppressing synoviocytes function and regulating immune cells responses in CIA rats, which might be associated with its ability to up-regulate the E-prostanoid (EP₄) receptor protein expression and modulate intracellular cAMP level.