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Journal of Experimental Pharmacology Volume 11, 2019 - Issue
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Original Research

Enhanced efficacy of chemically modified curcumin in experimental periodontitis: systemic implications

Howard H Wang1 Department of Periodontology and Endodontology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY, USA
,
Hsi-Ming Lee2 Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA
,
Veena Raja2 Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA
,
Wei Hou3 Department of Preventive Medicine, School of Medicine, Stony Brook University, Stony Brook, NY, USA
,
Vincent J Iacono4 Department of Periodontology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA
,
Joseph Scaduto5 Traverse Biosciences Inc., Stony Brook, NY, USA
,
Francis Johnson6 Department of Chemistry, Stony Brook University, Stony Brook, NY, USA;7 Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY, USA
,
Lorne M Golub2 Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA
&
Ying Gu8 Department of General Dentistry, School of Dental Medicine, Stony Brook University, Stony Brook, NY, USA, [email protected]Correspondence[email protected]
 show all
Pages 1-14 | Published online: 23 Jan 2019

Figures & data

Figure 1 The molecular structures of doxycycline (top), curcumin (middle), and CMC 2.24 [1,7-bis-(4-hydroxyphenyl)–4-phenylaminocarbonyl-1E,6E-heptadien-3,5-dione] (bottom).

Abbreviation: CMC, chemically modified curcumin.
Figure 1 The molecular structures of doxycycline (top), curcumin (middle), and CMC 2.24 [1,7-bis-(4-hydroxyphenyl)–4-phenylaminocarbonyl-1E,6E-heptadien-3,5-dione] (bottom).

Figure 2 Outline of experimental groups and timeline.

Abbreviation: LPS, lipopolysaccharide.
Figure 2 Outline of experimental groups and timeline.

Figure 3 Diagram indicating the positions of the key study region of maxillary molar teeth in rats at positions 6, 7, 8, and 9.

Abbreviations: ABC, alveolar bone crest; CEJ, cemento-enamel junction; M1, first molar; M2, second molar.
Figure 3 Diagram indicating the positions of the key study region of maxillary molar teeth in rats at positions 6, 7, 8, and 9.

Figure 4 (A) Effect of curcumin on levels of TNF-α secreted by human monocytes. Human peripheral blood-derived monocytes (1×106 cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without curcumin (2 or 5 µM). Conditioned medium was analyzed for TNF-α using ELISA. (B) Effect of CMC 2.24 on levels of TNF-α secreted by human monocytes. Human peripheral blood-derived monocytes (1×106cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without CMC 2.24 (2 or 5 µM). Conditioned medium was analyzed for TNF-α using ELISA. The * denotes that the difference is statistically significant with P<0.05.

Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide.
Figure 4 (A) Effect of curcumin on levels of TNF-α secreted by human monocytes. Human peripheral blood-derived monocytes (1×106 cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without curcumin (2 or 5 µM). Conditioned medium was analyzed for TNF-α using ELISA. (B) Effect of CMC 2.24 on levels of TNF-α secreted by human monocytes. Human peripheral blood-derived monocytes (1×106cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without CMC 2.24 (2 or 5 µM). Conditioned medium was analyzed for TNF-α using ELISA. The * denotes that the difference is statistically significant with P<0.05.

Figure 5 (A) Effect of curcumin on levels of IL-1β secreted by human monocytes. Human peripheral blood-derived monocytes (1×106 cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without curcumin (2 or 5 µM). Conditioned medium was analyzed for IL-1β using ELISA. (B) Effect of CMC 2.24 on levels of IL-1β secreted by human monocytes. Human peripheral blood-derived monocytes (1×106cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without CMC 2.24 (2 or 5 µM). Conditioned medium was analyzed for IL-1β using ELISA. The * denotes that the difference is statistically significant with P<0.05.

Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide.
Figure 5 (A) Effect of curcumin on levels of IL-1β secreted by human monocytes. Human peripheral blood-derived monocytes (1×106 cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without curcumin (2 or 5 µM). Conditioned medium was analyzed for IL-1β using ELISA. (B) Effect of CMC 2.24 on levels of IL-1β secreted by human monocytes. Human peripheral blood-derived monocytes (1×106cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without CMC 2.24 (2 or 5 µM). Conditioned medium was analyzed for IL-1β using ELISA. The * denotes that the difference is statistically significant with P<0.05.

Figure 6 Effect of curcumin or CMC 2.24 on levels of MMP-9 secreted by human monocytes.

Notes: Human monocytes (1×106 cells/well) were cultured in serum-free media (37°C, 5% CO2/95% O2, 18 hours) with LPS (50 ng/mL) and with or without curcumin or CMC 2.24. Conditioned medium was analyzed for MMP-9 by gelatin zymography. MMP-9 levels were quantitated by ImageJ. The * denotes that the difference is statistically significant with P<0.05.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide, MMP, matrix metalloproteinases.
Figure 6 Effect of curcumin or CMC 2.24 on levels of MMP-9 secreted by human monocytes.

Figure 7 (A) Gel zymogram of MMP-2 and MMP-9 levels in rat gingiva. (B) Quantification of MMP-2 in rat gingiva from gel zymogram. (C) Quantification of MMP-9 in rat gingiva from gel zymogram.

Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide, MMP, matrix metalloproteinases.
Figure 7 (A) Gel zymogram of MMP-2 and MMP-9 levels in rat gingiva. (B) Quantification of MMP-2 in rat gingiva from gel zymogram. (C) Quantification of MMP-9 in rat gingiva from gel zymogram.

Figure 8 IL-1β concentration in rat gingiva.

Note: Rat gingiva in each group were pooled and extracted with urea and analyzed for IL-1β using ELISA.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide.
Figure 8 IL-1β concentration in rat gingiva.

Figure 9 Activated MMP-9 levels in rat plasma.

Notes: Rat plasma were collected and analyzed through gelatin zymography. Levels of MMP-9 were quantified by ImageJ.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide, MMP, matrix metalloproteinases.
Figure 9 Activated MMP-9 levels in rat plasma.

Figure 10 MMP-2 levels in rat plasma.

Notes: Rat plasma were collected and analyzed through gelatin zymography. Levels of MMP-2 were quantified by ImageJ.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide, MMP, matrix metalloproteinases.
Figure 10 MMP-2 levels in rat plasma.

Figure 11 Representative periapical radiographs and morphometric images of each group.

Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide.
Figure 11 Representative periapical radiographs and morphometric images of each group.

Figure 12 Morphometric analysis of maxillary bone loss at positions 6, 7, 8, and 9 on both the buccal and palatal aspects between the first and second molars.

Note: The maxillae were defleshed, and bone loss was measured between first and second molars at positions 6, 7, 8, and 9.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide.
Figure 12 Morphometric analysis of maxillary bone loss at positions 6, 7, 8, and 9 on both the buccal and palatal aspects between the first and second molars.

Figure 13 Morphometric analysis of maxillary bone loss at positions 6, 7, 8, and 9only on the palatal aspect between the first and second molars.

Note: The maxillae were defleshed, and bone loss was measured between first and second molars at positions 6, 7, 8, and 9.
Abbreviations: CMC, chemically modified curcumin; LPS, lipopolysaccharide; NS, not significant.
Figure 13 Morphometric analysis of maxillary bone loss at positions 6, 7, 8, and 9only on the palatal aspect between the first and second molars.

Figure 14 Radiographic analysis of maxillary bone loss at positions 7 and 8 between the first and second molars.

Notes: The maxillae were defleshed, and bone loss between first and second molars was assessed radiographically using EMAGO dental imaging software at positions 7 and 8. Alveolar bone loss is defined as the distance between the CEJ and the alveolar bone crest.
Abbreviations: CEJ, cemento-enamel junction; CMC, chemically modified curcumin; LPS, lipopolysaccharide; NS, not significant.
Figure 14 Radiographic analysis of maxillary bone loss at positions 7 and 8 between the first and second molars.

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