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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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FACS analyses show that NEC selectively diminishes levels of blood monocytes.Leukocytes were isolated from whole blood collected from BALB/c mice (n = 6) before and 30 min after oral administration of NEC (1 g/kg). A, FACS analyses of leukocytes measuring the expression of cell surface markers: T-cells (CD3, CD4, or CD8), B-cells (B220), or monocytes (F4/80). * p≤0.05 versus time zero. B, Representative FACS analysis of F4/80+ expression.
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pone-0111559-g002: FACS analyses show that NEC selectively diminishes levels of blood monocytes.Leukocytes were isolated from whole blood collected from BALB/c mice (n = 6) before and 30 min after oral administration of NEC (1 g/kg). A, FACS analyses of leukocytes measuring the expression of cell surface markers: T-cells (CD3, CD4, or CD8), B-cells (B220), or monocytes (F4/80). * p≤0.05 versus time zero. B, Representative FACS analysis of F4/80+ expression.

Mentions: While the molecular signaling of curcumin in cells and its effects as an anti-inflammatory mediator in vivo have been previously investigated, studies examining the differential effects of curcumin on immune cell subtypes in modulating these responses have remained largely unexplored. To assess whether curcumin can differentially influence immune cell subtypes, BALB/c mice were orally administered with NEC; purified leukocytes were isolated from whole blood after 30 min and analyzed by flow cytometry. Markers for T-cells (CD3, CD4, and CD8), B-cells (B220), and macrophages (F4/80) were used in flow assisted cell sorting (FACS) analyses to measure levels of each subtype. When compared to baseline measurements, CD3+, CD4+, CD8+, and B220+ cells were unchanged, but levels of F4/80+ cells were significantly reduced by 2.2-fold (p≤0.01) with NEC treatment (Figure 2A). FACS plots of the total leukocyte population also showed NEC-mediated reduction of F4/80+ macrophages in blood circulation (Figure 2B).


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)

FACS analyses show that NEC selectively diminishes levels of blood monocytes.Leukocytes were isolated from whole blood collected from BALB/c mice (n = 6) before and 30 min after oral administration of NEC (1 g/kg). A, FACS analyses of leukocytes measuring the expression of cell surface markers: T-cells (CD3, CD4, or CD8), B-cells (B220), or monocytes (F4/80). * p≤0.05 versus time zero. B, Representative FACS analysis of F4/80+ expression.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111559-g002: FACS analyses show that NEC selectively diminishes levels of blood monocytes.Leukocytes were isolated from whole blood collected from BALB/c mice (n = 6) before and 30 min after oral administration of NEC (1 g/kg). A, FACS analyses of leukocytes measuring the expression of cell surface markers: T-cells (CD3, CD4, or CD8), B-cells (B220), or monocytes (F4/80). * p≤0.05 versus time zero. B, Representative FACS analysis of F4/80+ expression.
Mentions: While the molecular signaling of curcumin in cells and its effects as an anti-inflammatory mediator in vivo have been previously investigated, studies examining the differential effects of curcumin on immune cell subtypes in modulating these responses have remained largely unexplored. To assess whether curcumin can differentially influence immune cell subtypes, BALB/c mice were orally administered with NEC; purified leukocytes were isolated from whole blood after 30 min and analyzed by flow cytometry. Markers for T-cells (CD3, CD4, and CD8), B-cells (B220), and macrophages (F4/80) were used in flow assisted cell sorting (FACS) analyses to measure levels of each subtype. When compared to baseline measurements, CD3+, CD4+, CD8+, and B220+ cells were unchanged, but levels of F4/80+ cells were significantly reduced by 2.2-fold (p≤0.01) with NEC treatment (Figure 2A). FACS plots of the total leukocyte population also showed NEC-mediated reduction of F4/80+ macrophages in blood circulation (Figure 2B).

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