Protective effects of paeonol on inflammatory response in IL-1 beta-induced human fibroblast-like synoviocytes and rheumatoid arthritis progression via modulating NF-kappa B pathway

摘要

Various investigations have demonstrated that human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) take part in the chronic inflammatory responses and RA progression. Inhibition of synovium activation and inflammatory processes may represent a therapeutic target to alleviate RA. Paeonol, a major natural product, has many biological and pharmacological activities. However, its protective effects against RA considering HFLS-RA have not been explored. In this study, anti-inflammatory effects of paeonol were detected in interleukin-1 beta (IL-1 beta)-treated HFLS-RA. Our results demonstrated that paeonol had no effect on cell survival and IL-1 beta-induced proliferation in HFLS-RA. Pretreatment with paeonol significantly suppressed the production of pro-inflammatory TNF-alpha, IL-6 and IL-1 beta, and the expressions of matrix metalloproteinase-1/-3 in vitro and in vivo. Mice treated with paeonol (10 mg/kg) remarkablely attenuated arthritic symptoms based on clinical arthritis scores and histopathology in collagen-induced arthritis mice. Furthermore, the TLR4 expression and NF-kappa B p65 activation were inhibited by paeonol in vitro and in vivo. Our findings illustrated that paeonol had significantly suppressed inflammation effects in synovial tissues and RA progression. The potential mechanism might be based on the attenuation TLR4-NF-kappa B activation. These collective results indicated that paeonol might be a promising therapeutic agent for alleviating RA progress through inhibiting inflammations and NF-kappa B signalling pathway.