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1544104 
Journal Article 
The synergistic anti-inflammatory effects of lycopene, lutein, beta-carotene, and carnosic acid combinations via redox-based inhibition of NF-kappa B signaling 
Hadad, N; Levy, R 
2012 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
53 
7 
1381-1391 
English 
22889596 
WOS:000309575300001 
Inflammatory mediators and cytokines play important roles
in the pathogenesis of a vast number of human diseases: therefore much attention is focused on
blunting their proinflammatory modes of action. The aims of the present research were to assess
the effectiveness of combinations of carotenoids and phenolics, at concentrations that can be
achieved in blood, to inhibit the release of inflammatory mediators from macrophages exposed to
lipopolysaccharide (LPS) and to determine what the anti-inflammatory effect of the phytonutrient
combinations was in an in vivo mouse model of peritonitis. Preincubation of mouse peritoneal
macrophages with lycopene (1 mu M) or Lyc-O-Mato (1 mu M) and carnosic acid (2 mu M), lutein (1
mu M), and/or beta-carotene (2 mu M) 1 h before addition of LPS for 24 h caused a synergistic
inhibition of NO, prostaglandin E-2, and superoxide production derived from down-regulation of
iNOS, COX-2, and NADPH oxidase protein and mRNA expression and synergistic inhibition of TNF
alpha. secretion. We surmise that the anti-inflammatory action of the phytonutrient combinations
used probably resides in their antioxidant properties, because they caused an immediate,
efficient, and synergistic inhibition of LPS-induced internal superoxide production leading to a
marked decrease in ERK and NF-kappa B activation. The anti-inflammatory effects of the selected
phytonutrient combinations were also demonstrated in a mouse model of peritonitis: their
supplementation in drinking water resulted in attenuation of neutrophil recruitment to the
peritoneal cavity and in inhibition of inflammatory mediator production by peritoneal neutrophils
and macrophages. (C) 2012 Elsevier Inc. All rights reserved. 
Lycopene; NOX2-NADPH oxidase; Proinflammatory mediators; Carotenoids; Polyphenols; Free radicals