Rheumatology: Current Research
Open Access
ISSN: 2161-1149 (Printed)
+44-20-4587-4809
ISSN: 2161-1149 (Printed)
+44-20-4587-4809
Syahida Ahmad
Universiti Putra Malaysia, Malaysia
Posters & Accepted Abstracts: Rheumatology
Statement of the Problem: Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. Our preliminary findings had shown that the newly synthesized curcumin analogue [2,6-bis(2,5- dimethoxybenzylidene) cyclohexanone] or BDMC33 exhibited improved anti-inflammatory activity by inhibiting nitric oxide synthesis, PGE2 synthesis and cyclooxygenase (COX) expression in activated macrophage cells. Aim: Aim of this study was to investigate the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) in vitro. Methodology & Theoretical Orientation: Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12- myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-KB) activation by using various bioassay methods, including zymography, western blotting, reverse transcription polymerase chain reaction, immunofluorescence microscopy and electrophoretic mobility shift assay. Results: The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-KB nuclear translocation and NF-KB DNA binding activity in PMA-stimulated SF. Conclusion & Significance: BDMC33 represents an effective chemo-preventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention.
Email: syahida@upm.edu.my