Amelioration of Carrageenan/Kaolin-Induced Arthritis by Benzylideneacetophenone Derivatives in Rats.

Abstract

This study was done to evaluate the inhibitory effects of benzylideneacetophenone derivatives (JCII) on rheumatoid arthritis (RA). This was done by using carrageenan/kaolin-induced arthritis in rats and human RA fibroblast-like synoviocytes (FLS). In FLS cells and Jurkat T cells, JCII compounds at 5, 10, and 20 μM were used to treat the cells followed by stimulation with IL-1β (10 ng/mL) for FLS cells and PMA/A23187 for Jurkat T cells. Inflammatory mediators and cytokines related to activated T cell functions were then analyzed using RT-PCR and ELISA. In rats, JCII compounds at 1, 5, and 10 mg/kg were given intraperitoneally daily for 6 days. Thereafter, arthritis evaluation was conducted by measuring squeaking scores, knee thickness, and WDR as well as histological assessments of the knee joints. Inflammatory mediators were also measured in the serum of the rats. JCII compounds given at 10 mg/kg significantly alleviated arthritis symptoms especially on day 5 or day 6 following arthritis in rats. The histological results were found to be consistent with the behavioral evaluation that were measured. In stimulated FLS cells, the same pattern was seen wherein JCII compounds also decreased the levels of different inflammatory mediators and MMPs. Also, the phosphorylation of JNK and p38 MAPK pathways were inhibited by JCII compounds. In addition, the level of TNF-α from activated T cells were downregulated by JCII treatment. These show that JCII compounds show a potential anti-arthritic effect at least via anti-inflammation and can be used potentially for the treatment in arthritis and the accompanying inflammatory disease.