Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

PLoS One. 2015 Dec 30;10(12):e0145539. doi: 10.1371/journal.pone.0145539. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / metabolism*
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism*
  • Humans
  • Inflammation / metabolism
  • Metabolomics / methods
  • Middle Aged
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Curcumin

Grant support

This work was supported by the Advanced Biomass R&D Center of Korea (http://www.biomass.re.kr/en, 2011-0031353) to KHK, the National Research Foundation of Korea funded by the Ministry of Education (http://www.nrf.re.kr/nrf_eng_cms/, NRF-2013R1A1A2059103) to HSC, and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare (http://www.khidi.or.kr/kps, HI14C2285) to HSC, which are funded by the Korean Government. Experiments were performed using facilities of the Institute of Biomedical Science and Food Safety at the Korea University Food Safety Hall.