Chemopreventive effects of a curcumin‐like diarylpentanoid [2,6‐bis(2,5‐dimethoxybenzylidene)cyclohexanone] in cellular targets of rheumatoid arthritis in vitro

• Main Authors: Lee, Ka Heng, Abas, Faridah, Mohammed Alitheen, Noorjahan Banu, Shaari, Khozirah, Lajis, Nordin, Israf Ali, Daud Ahmad, Ahmad, Syahida
• Format: Article
• Language: English
• Published: Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia 2015
• Online Access: http://psasir.upm.edu.my/id/eprint/36780/1/36780.pdf; http://psasir.upm.edu.my/id/eprint/36780/; https://onlinelibrary.wiley.com/doi/abs/10.1111/1756-185X.12341

Aim: Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC 33 (2,6‐bis[2,5‐dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti‐inflammatory activity has been synthesized and the potency of BDMC 33 on molecular and cellular basis of synovial fibroblasts (SF ) were evaluated in vitro. Methods: Synovial fibroblast cells (HIG ‐82) were cultured in vitro and induced by phorbol‐12‐myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMP s) and pro‐inflammatory cytokines. The protective effects of BDMC 33 were evaluated toward MMP activities, pro‐inflammatory cytokine expression and nuclear factor kappa‐B (NF ‐κB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescense microscopy and electrophoretic mobility shift assay. Results: The results showed that BDMC 33 significantly inhibited the pro‐gelatinase B (pro‐MMP ‐9) and collagenase activities via suppression of MMP ‐1 in activated SF. In addition, BDMC 33 strongly suppressed MMP‐3 gene expression as well as inhibited COX‐2 and IL‐6 pro‐inflammatory gene expression. We also demonstrated that BDMC 33 abolished the p65 NF‐κB nuclear translocation and NF‐κB DNA binding activity in PMA ‐stimulated SF. Conclusions: BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention.