Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial
inflammation and joint disability.
Curcumin is known to be effective in ameliorating joint
inflammation in RA. To obtain new insights into the effect of
curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of
tumor necrosis factor (TNF)-α-stimulated and
curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or
curcumin). Treatment of FLS with
curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent.
Curcumin-treated FLS had higher restoration of
amino acid and
fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of
amino acid and
fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of
glycine,
citrulline,
arachidonic acid, and
saturated fatty acids in TNF-α-stimulated FLS was restored to the control level
after treatment with
curcumin, suggesting that the effect of
curcumin on preventing joint
inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of
curcumin and new targets for therapeutic drugs in RA.