P26 Tamaractam, a natural lactam, induces apoptosis and inhibits inflammation in rheumatoid arthritis fibroblast-like synoviocytes

Tamaractam is a novel lactam isolated from Tamarix ramosissima Ledeb., a traditional herbal medicine used for rheumatoid arthritis (RA) treatment in northwest China. The present study investigated the pro-apoptotic and anti-inflammatory effects of tamaractam on fibroblast-like synoviocytes (FLS) from RA patients. Apoptosis was assessed by TUNEL assay and caspase-3 activity was assessed by a colorimetric assay. The expression levels of apoptosis-related proteins including Bcl-2, Bax, p-Akt and p53 were determined by western blot analyses. The levels of IL-1β, IL-6, MMP-9 and COX-2 were measured using ELISA, and the mRNA expressions of these pro-inflammatory mediators were measured with quantitative real-time PCR. Tamaractam (0.1 and 1 μM) treatment induced cellular apoptosis of RA-FLS and also resulted in a significant increase in caspase-3 activity. It was found that tamaractam could regulate the protein expression of Bcl-2, Bax, p53 and pAkt. The concentrations and mRNA expression levels of IL-1β, IL-6, MMP-9 and COX-2 from RA-FLS were suppressed by tamaractam treatment in a dose-dependent manner. In conclusion, tamaractam treatment was found to induce apoptosis of RA-FLS through regulation of apoptosis related protein expression and to reduce the level of pro-inflammatory factors through inhibition of pro-inflammatory gene expression in RA-FLS. These results suggest that the pro-apoptotic and anti-inflammatory activities of tamaractam may be used as a possible therapeutic option for RA.