title: Oral administration of nano-emulsion curcumin in mice suppresses inflammatory-induced NFκB signaling and macrophage migration.
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.
authors.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.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Young
authors.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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Bruss
authors.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.
authors.forename: Mark
authors.initials: M
authors.lastname: Gardner
authors.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.
authors.forename: William L
authors.initials: WL
authors.lastname: Willis
authors.affiliation: Center for Biostatistics, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.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.
authors.forename: Giancarlo R
authors.initials: GR
authors.lastname: Valiente
authors.affiliation: College of Pharmacy, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Pharmacy, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America; Comprehensive Cancer Center, Wexner Medical Center at The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Liu
authors.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.
authors.forename: Wael N
authors.initials: WN
authors.lastname: Jarjour
authors.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.
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D004655:Emulsions; D008070:Lipopolysaccharides; D016328:NF-kappa B; D003474:Curcumin