Paeonol inhibits IL-1β induced expression of iNOS, COX-2, and MMPs through NF-κB activation: an in vitro and in vivo study

Introduction: Paeonol (2'-hydroxy-4'-methoxyacetophenone) is a common traditional Chinese remedy that possesses diverse biological activities, including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In the present study, we investigated the anti-inflammatory properties of paeonol in chondrocytes. Methods: We assessed the effects of paeonol on MMPs, iNOS and COX-2 mRNA expression by quantitative real-time PCR and western blot in IL-1 beta-induced rabbit chondrocytes and evaluated the in vivo effects of paeonol in an experimental OA model in rabbits. The NO production was determined by Griess method, the PGE(2) production was detected by ELISA. Western blot and PCR were performed to investigate the protein level of inhibitor of I kappa B-alpha and the translocation of NF-kappa B. Results: We found that paeonol inhibited the production of PGE(2) and NO induced by IL-1 beta and significantly decreased IL-1 beta-stimulated gene expression and production of MMPs, iNOS and COX-2 in rabbit chondrocytes. Paeonol inhibited IL-1 beta-mediated activation of NF-kappa B by suppressing degradation of I kappa B alpha in the cytoplasm. In rabbits, morphological and histological analyses determined that paeonol decreased cartilage degradation. Downregulation of MMP-1, MMP-3, MMP-13, iNOS and COX-2 expression and up-regulation of TIMP-1 expression were also detected in paeonol-treated cartilage compared with the control group, confirming these findings in an in vivo model. Conclusions: These findings suggest that paeonol may be a potential agent in the treatment of OA.