title: Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.
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.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Joong Kyong
authors.initials: JK
authors.lastname: Ahn
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Sooah
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, National Police Hospital, Seoul, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Jungyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea.
authors.forename: You Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Rheumatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Koh
authors.affiliation: Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea.
authors.forename: Kyoung Heon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Rheumatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hoon-Suk
authors.initials: HS
authors.lastname: Cha
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin