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Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

Young NA, Bruss MS, Gardner M, Willis WL, Mo X, Valiente GR, Cao Y, Liu Z, Jarjour WN, Wu LC - PLoS ONE (2014)

Bottom Line: Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential.Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1.These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT
Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

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Related in: MedlinePlus

NEC suppresses LPS-induced TLR4 and RAGE expression in addition to blood monocyte accumulation.BALB/c mice (n = 10) were treated with NEC (1 g/kg) or vehicle by oral gavage and injected with LPS (IP, 2 mg/kg) 10 min afterward. At 4 h, whole blood was collected and leukocytes were isolated for flow cytometry. A, Quantitation (top) and representative images (bottom) from FACS analysis to measure F4/80+ cells. B, FACS analysis measuring TLR2, RAGE, or TLR4 expression on the surface of cells. C, ELISA of MCP-1 expression from mouse serum. *  =  p≤0.05 versus vehicle. IP  =  intraperitoneal.
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pone-0111559-g003: NEC suppresses LPS-induced TLR4 and RAGE expression in addition to blood monocyte accumulation.BALB/c mice (n = 10) were treated with NEC (1 g/kg) or vehicle by oral gavage and injected with LPS (IP, 2 mg/kg) 10 min afterward. At 4 h, whole blood was collected and leukocytes were isolated for flow cytometry. A, Quantitation (top) and representative images (bottom) from FACS analysis to measure F4/80+ cells. B, FACS analysis measuring TLR2, RAGE, or TLR4 expression on the surface of cells. C, ELISA of MCP-1 expression from mouse serum. *  =  p≤0.05 versus vehicle. IP  =  intraperitoneal.

Mentions: To examine the influence of NEC on macrophage accumulation in the context of an acute inflammatory response, we stimulated wild-type BALB/c mice with LPS and blood was collected for FACS analysis after 4 h. In agreement with the data shown in Figure 2, oral administration of NEC diminished blood accumulation of F4/80+ cells (4-fold; p≤0.05) in the total leukocyte population with LPS stimulation (Figure 3A).


Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.

Young NA, Bruss MS, Gardner M, Willis WL, Mo X, Valiente GR, Cao Y, Liu Z, Jarjour WN, Wu LC - PLoS ONE (2014)

NEC suppresses LPS-induced TLR4 and RAGE expression in addition to blood monocyte accumulation.BALB/c mice (n = 10) were treated with NEC (1 g/kg) or vehicle by oral gavage and injected with LPS (IP, 2 mg/kg) 10 min afterward. At 4 h, whole blood was collected and leukocytes were isolated for flow cytometry. A, Quantitation (top) and representative images (bottom) from FACS analysis to measure F4/80+ cells. B, FACS analysis measuring TLR2, RAGE, or TLR4 expression on the surface of cells. C, ELISA of MCP-1 expression from mouse serum. *  =  p≤0.05 versus vehicle. IP  =  intraperitoneal.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219720&req=5

pone-0111559-g003: NEC suppresses LPS-induced TLR4 and RAGE expression in addition to blood monocyte accumulation.BALB/c mice (n = 10) were treated with NEC (1 g/kg) or vehicle by oral gavage and injected with LPS (IP, 2 mg/kg) 10 min afterward. At 4 h, whole blood was collected and leukocytes were isolated for flow cytometry. A, Quantitation (top) and representative images (bottom) from FACS analysis to measure F4/80+ cells. B, FACS analysis measuring TLR2, RAGE, or TLR4 expression on the surface of cells. C, ELISA of MCP-1 expression from mouse serum. *  =  p≤0.05 versus vehicle. IP  =  intraperitoneal.
Mentions: To examine the influence of NEC on macrophage accumulation in the context of an acute inflammatory response, we stimulated wild-type BALB/c mice with LPS and blood was collected for FACS analysis after 4 h. In agreement with the data shown in Figure 2, oral administration of NEC diminished blood accumulation of F4/80+ cells (4-fold; p≤0.05) in the total leukocyte population with LPS stimulation (Figure 3A).

Bottom Line: Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential.Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1.These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology and Immunology, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America; Department of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.

ABSTRACT
Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

Show MeSH
Related in: MedlinePlus