Mangiferin: A promising therapeutic agent for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Despite aggressive treatment with anti-rheumatic drugs, progressive destruction of joints continues to occur in RA patients, who subsequently require joint surgery. A lot of evidence suggest that fibroblast-like synovial cells (FLS) play crucial role in joint degradation and the propagation of inflammation in RA. The expansion of fibroblast populations in the joint results primarily from the inhibition of pro-apoptotic pathways, rather than large scale proliferation. Because multiple factors, which contribute to fibroblast activation and enhance their destructive potential, are under control of transcription factor NF-κB, this pathway presents an interesting target for RA therapy. However, due to the lack of specificity, NF-κB inhibitors may exert severe side effects. Given the above, there has recently been more interest in natural substances of plant origin which are regarded as a safe alternatives for synthetic drugs. Mangiferin, the naturally occurring polyphenol with excellent anti-inflammatory and antioxidative properties, exhibits strong pro-apoptotic effect toward synoviocytes isolated from human synovia. Moreover, it shows no cytotoxicity toward cultivated chondrocytes and reduces the levels of matrix metalloproteinases. Considering that mangiferin is a natural constituent of foods and traditional herbal medicines, showing fewer adverse effects and low toxicity, we hypothesize that it may prove effective in the treatment of RA and prevention against joint destruction.