V. Ivanov, J. Cha, S. Ivanova, T. Kalinofsky, M.W. Roomi, M. Rath, A. Niedzwiecki
International Journal of Molecular Medicine 2008; 22(6): 731-741
We investigated the effects of a nutrient mixture (NM) including ascorbic acid, quercetin, naringenin, hesperetin, tea catechins, lysine, proline, arginine and N-acetyl cysteine in experimental in-vivo and in-vitro inflammation triggered by bacterial lipopolysaccharide (LPS). BALB/c mice (n=36) were supplemented with 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), specific mRNA levels (RT-PCR), and nuclear factor kappa beta (NFkB) activation (phosphorylated p65 immunoassay). Nutrient supplementation in mice altered 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 in vivo study (r=0.718, p=0.023). NM inhibited COX2 enzymatic activity and COX2 and pro-inflammatory cytokine protein expressions were downregulated by NM at transcription level complementing a blockade in NFkB activation. NM demonstrated strong beneficial effects in experimental inflammation by targeting multiple responsible mechanisms in a complex process of inflammatory reaction to pathogens.
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