title: Essential nutrients suppress inflammation by modulating key inflammatory gene expression.
abstract: We investigated the effects of a nutrient mixture (NM) consisting of ascorbic acid, quercetin, naringenin, hesperetin, tea catechins, lysine, proline, arginine and N-acetylcysteine on experimental in vivo and in vitro inflammation triggered by bacterial lipopolysaccharide (LPS). BALB/c mice (n=36) were administered NM (200 mg/kg BW) or ibuprofen (20 mg/kg BW) for two weeks. Blood plasma, collected three hours after a single intraperitoneal injection with LPS (1 mg/kg BW), was analyzed with 14 cytokine microarray. LPS inflammatory effects were analyzed in human U937 macrophages by cytokine release, cyclooxygenase (COX) enzymatic activity, COX protein expression (Western blot analysis), specific mRNA levels (RT-PCR), and nuclear factor kappabeta (NFkappabeta) activation (phosphorylated p65 immunoassay). Nutrient supplementation in mice altered the LPS-induced cytokine response in a manner similar to ibuprofen (r=0.4157, p=0.139). Cytokine response to LPS in cultured macrophages was similar to the in vivo study (r=0.718, p=0.023). NM inhibited COX-2 enzymatic activity, and COX-2 and pro-inflammatory cytokine protein expression levels were downregulated by NM at the transcription level complementing a blockade in NFkappabeta activation. NM demonstrated strong beneficial effects on the experimental inflammation by targeting multiple responsible mechanisms in the complex process involved in the inflammatory reaction to pathogens.
authors.affiliation: Dr Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: V
authors.initials: V
authors.lastname: Ivanov
authors.forename: J
authors.initials: J
authors.lastname: Cha
authors.forename: S
authors.initials: S
authors.lastname: Ivanova
authors.forename: T
authors.initials: T
authors.lastname: Kalinovsky
authors.forename: M W
authors.initials: MW
authors.lastname: Roomi
authors.forename: M
authors.initials: M
authors.lastname: Rath
authors.forename: A
authors.initials: A
authors.lastname: Niedzwiecki
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019587:Dietary Supplements; D015232:Dinoprostone / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D051996:Transcription Factor RelA / Q000378:metabolism; D020298:U937 Cells
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D016753:Interleukin-10; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D007052:Ibuprofen