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

Ahn JK, Kim S, Hwang J, Kim J, Lee YS, Koh EM, Kim KH, Cha HS - PLoS ONE (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

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.

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Hierarchical clustering analysis of 119 identified metabolites from RA FLS.The results of heat mapping generated through metabolomic analysis and the relevant changes discovered. A heat map showed that the metabolite profiles of controls were similar to those of the curcumin-treated group. Red color reflects an increase, and blue color a decrease.
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pone.0145539.g002: Hierarchical clustering analysis of 119 identified metabolites from RA FLS.The results of heat mapping generated through metabolomic analysis and the relevant changes discovered. A heat map showed that the metabolite profiles of controls were similar to those of the curcumin-treated group. Red color reflects an increase, and blue color a decrease.

Mentions: A total of 119 identified metabolites were clustered and visualized by the HCA using the Euclidean distance and average linkage method to determine possible variations in the metabolite profiling of the three groups (Fig 2). The clustering of the metabolites led to good separation among the three groups. Similar metabolic patterns were shown between the control and curcumin-treated group. On the other hand, a clear separation of the metabolic profile of the TNF-α-stimulated group from the control and curcumin-treated groups was shown. This indicated that the metabolic pattern of the TNF-α-stimulated group was completely different from those of the control and curcumin-treated groups, similar to the PCA result.


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

Ahn JK, Kim S, Hwang J, Kim J, Lee YS, Koh EM, Kim KH, Cha HS - PLoS ONE (2015)

Hierarchical clustering analysis of 119 identified metabolites from RA FLS.The results of heat mapping generated through metabolomic analysis and the relevant changes discovered. A heat map showed that the metabolite profiles of controls were similar to those of the curcumin-treated group. Red color reflects an increase, and blue color a decrease.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696817&req=5

pone.0145539.g002: Hierarchical clustering analysis of 119 identified metabolites from RA FLS.The results of heat mapping generated through metabolomic analysis and the relevant changes discovered. A heat map showed that the metabolite profiles of controls were similar to those of the curcumin-treated group. Red color reflects an increase, and blue color a decrease.
Mentions: A total of 119 identified metabolites were clustered and visualized by the HCA using the Euclidean distance and average linkage method to determine possible variations in the metabolite profiling of the three groups (Fig 2). The clustering of the metabolites led to good separation among the three groups. Similar metabolic patterns were shown between the control and curcumin-treated group. On the other hand, a clear separation of the metabolic profile of the TNF-α-stimulated group from the control and curcumin-treated groups was shown. This indicated that the metabolic pattern of the TNF-α-stimulated group was completely different from those of the control and curcumin-treated groups, similar to the PCA result.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Rheumatology, Kangbuk Samsung hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus