Anti-inflammatory Potential of Thymoquinone in Tumor Necrosis Factor-alpha Stimulated SW982 Human Synovial Fibroblasts

INTRODUCTION: Rheumatoid arthritis is a common systemic autoimmune disease characterized by chronic inflammation of the joints that can induce the formation of pannus tissue and ultimately leads to joint destruction. Thymoquinone, the major bioactive constituent of Nigella sativa seed oil has diverse pharmacological properties. Although there are some studies in the literature showing the anti-inflammatory activity of thymoquinone, it is not yet clear whether thymoquinone can prevent inflammation caused by rheumatoid arthritis. The goal of this study was to investigate the potential anti-inflammatory effects of thymoquinone treatment on synovial fibroblasts.
METHODS: In our study, we investigated the effects of thymoquinone on nitric oxide production, interleukine-6 (IL-6), IL-8, and prostaglandin E2 (PGE2) levels, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor receptor-1 (TNF-R1), and TNF-R2 protein expressions, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and Akt phosphorylation levels in tumor necrosis factor-alpha (TNF-α) stimulated SW982 human synovial fibroblasts.
RESULTS: Thymoquinone treatment (0-1 µM) resulted in significant and concentration-dependently reduced the TNF-α stimulated production of nitric oxide, IL-6, IL-8, and PGE2 levels compared to the untreated group (p<0.05). Also thymoquinone treatment in high concentrations exerted an anti-inflammatory effect by suppressing iNOS, COX-2, TNF-R1, and TNF-R2 protein expressions and the phosphorylation of JNK, p38 MAPK, ERK1/2 and Akt in SW982 synovial fibroblasts (p<0.05).
DISCUSSION AND CONCLUSION: Taken together, these results show that thymoquinone in high concentrations is able to play a beneficial role in TNF-α mediated signaling in rheumatoid arthritis synovial fibroblasts.