ABSTRACT

Objective: Metformin is well known anti-diabetic agent. Recently many reports have described the anti-inflammatory effects of metformin on various cell types including human vascular smooth muscle cells and endothelial cells. This study was designed to investigate the anti-arthritic effects of metformin on Freund’s complete adjuvant (FCA)-induced arthritis in rats. Methods: rats were randomly divided into 4 groups as follows: control group, rheumatoid arthritis (RA) rat model group, indomethacin group and metformin group. The hind paw volume of rats was measured. Oxidative stress and inflammatory cytokines were also analyzed. Western blot analysis was used to evaluate cyclooxygenase-2 (COX-2) protein expression levels. Results: The results demonstrated that metformin (200 mg kg-1) was able significantly to reduce hind paw volume. Metformin treatment decreased circulating levels of inflammatory response markers C-reactive protein (CRP), IL-1β, IL-6 and TNF-α. The production of COX-2 and subsequently prostaglandin E2 (PGE2) in FCA rats was reduced significantly by treatment with metformin. In addition, metformin significantly reduced oxidative stress. Conclusion: These findings suggest that the inflammatory response and oxidative stress induced by FCA could be attenuated by metformin in RA rat model. Metformin has significant anti-inflammatory effects on FCA rats, which may be associated with the reduction of COX-2 and PGE2 inflammatory mediators.