Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes

Objectives: To investigate whether gallic acid (3, 4, 5-trihydroxybenzoic acid), a natural polyphenolic acid found in gall nuts, sumac, oak bark, tea leaves, grapes and wine, has pro-apoptotic and anti-inflammatory effects on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Methods: Viability of RA FLS was assessed using a MTT assay after gallic acid treatment. Apoptosis was assessed by TUNEL assay and caspase-3 activity was determined by a colorimetric assay. The levels of apoptosis-related proteins including Bcl-2, p-Akt, p53, and Bax were determined using western blot analyses, and the mRNA expressions of various pro-inflammatory mediators were measured using quantitative real-time PCR. Results: Cell viability of RA FLS was significantly decreased by treatment with 10 or more mu M of gallic acid. Gallic acid treatment at the concentrations that do not affect cell viability (0.1 and 1 mu M) induced cellular apoptosis of RA FLS. Treatment with 0.1 and 1 mu M of gallic acid also resulted in a significant increase in caspase-3 activity and regulated the productions of Bcl-2, Bax, p53 and pAkt. The mRNA expression levels of pro-inflammatory cytokines (IL-1 beta, IL-6), chemokines (CCL-2/MCP-1, CCL-7/MCP-3), cyclooxygenase-2, and matrix metalloproteinase-9 from RA FLS were suppressed by the gallic acid treatment in dose-dependent manners. Conclusion: Gallic acid treatment was found to induce apoptosis of RA FLS through regulation of apoptosis-related protein expressions and to reduce the expression of pro-inflammatory genes in RA FLS. These data suggest that pro-apoptotic and anti-inflammatory activities of gallic acid may be used as a possible therapeutic option for RA. (C) 2012 Published by Elsevier Masson SAS on behalf of the Societe Francaise de Rhumatologie.