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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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PCA score (A) and loading plots (B) of RA fibroblast-like synoviocytes (FLS), which were not stimulated (Control), stimulated with TNF-α (TNF), and treated with curcumin (Curcumin).(A) Principal component (PC)1 explained the significant separation of metabolite profiles between the TNF-α-stimulated group on the negative region of the PC1, and the control and curcumin-treated groups on the positive region of the PC1. Further, the control group was clearly separated from the curcumin-treated group on PC2. (B) PC1 was explained by 84 metabolites that correlated positively with the axis, and 35 metabolites that correlated negatively.
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pone.0145539.g001: PCA score (A) and loading plots (B) of RA fibroblast-like synoviocytes (FLS), which were not stimulated (Control), stimulated with TNF-α (TNF), and treated with curcumin (Curcumin).(A) Principal component (PC)1 explained the significant separation of metabolite profiles between the TNF-α-stimulated group on the negative region of the PC1, and the control and curcumin-treated groups on the positive region of the PC1. Further, the control group was clearly separated from the curcumin-treated group on PC2. (B) PC1 was explained by 84 metabolites that correlated positively with the axis, and 35 metabolites that correlated negatively.

Mentions: After the normalization by the sum of peak intensity of identified metabolites, multivariate statistical modeling using PCA was performed on mass spectral data. The PCA model showed a variation value (R2X) of 0.73 and predictive capability (Q2) of 0.81, indicating the excellence of the PCA model. From the PCA score plots, the metabolite profiles were clearly separated between the three groups (i.e., control, TNF-α-stimulated, and curcumin-treated FLS) (Fig 1A). The principal component (PC) 1 had the largest possible variation (55.6%) between these three groups, explaining the significant separation of metabolite profiles between TNF-α-stimulated group and the control and curcumin-treated group. These results indicated that the metabolite profiles of RA FLS were altered by TNF-α and the altered metabolic pattern of TNF-α-stimulated FLS was recovered to that of control group by curcumin treatment.


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)

PCA score (A) and loading plots (B) of RA fibroblast-like synoviocytes (FLS), which were not stimulated (Control), stimulated with TNF-α (TNF), and treated with curcumin (Curcumin).(A) Principal component (PC)1 explained the significant separation of metabolite profiles between the TNF-α-stimulated group on the negative region of the PC1, and the control and curcumin-treated groups on the positive region of the PC1. Further, the control group was clearly separated from the curcumin-treated group on PC2. (B) PC1 was explained by 84 metabolites that correlated positively with the axis, and 35 metabolites that correlated negatively.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0145539.g001: PCA score (A) and loading plots (B) of RA fibroblast-like synoviocytes (FLS), which were not stimulated (Control), stimulated with TNF-α (TNF), and treated with curcumin (Curcumin).(A) Principal component (PC)1 explained the significant separation of metabolite profiles between the TNF-α-stimulated group on the negative region of the PC1, and the control and curcumin-treated groups on the positive region of the PC1. Further, the control group was clearly separated from the curcumin-treated group on PC2. (B) PC1 was explained by 84 metabolites that correlated positively with the axis, and 35 metabolites that correlated negatively.
Mentions: After the normalization by the sum of peak intensity of identified metabolites, multivariate statistical modeling using PCA was performed on mass spectral data. The PCA model showed a variation value (R2X) of 0.73 and predictive capability (Q2) of 0.81, indicating the excellence of the PCA model. From the PCA score plots, the metabolite profiles were clearly separated between the three groups (i.e., control, TNF-α-stimulated, and curcumin-treated FLS) (Fig 1A). The principal component (PC) 1 had the largest possible variation (55.6%) between these three groups, explaining the significant separation of metabolite profiles between TNF-α-stimulated group and the control and curcumin-treated group. These results indicated that the metabolite profiles of RA FLS were altered by TNF-α and the altered metabolic pattern of TNF-α-stimulated FLS was recovered to that of control group by curcumin treatment.

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