Macrophages in oxidative stress and models to evaluate the antioxidant function of dietary natural compounds

Abstract

Antioxidant testing of natural products has attracted increasing interest in recent years, mainly due to the fact that an antioxidant-rich diet might provide health benefits. Activated macrophages are a major source of reactive oxygen species, reactive nitrogen species, and peroxynitrite generated through the so-called respiratory burst. Constitutively released proinflammatory cytokine, especially tumor necrosis factor-α, triggers nuclear factor-κB, and activator protein-1 translocation leading to the over production of reactive oxygen species and reactive nitrogen species in macrophages. Activation of transcription factors in the long-lived tissue-resident macrophages and/or monocyte-derived macrophages, trigger epigenetic modifications leading to the pathogenesis of chronic diseases. Nutraceuticals including lipid raft structure disruption agent, cholesterol depletion agent, farnesyltransferase inhibitor, nuclear factor-κB blocker (α,β-unsaturated carbonyl compounds), glucocorticoid receptor agonist, and peroxisome proliferator-activated receptor-γ agonist have long been used to inactive macrophage. The inhibition effects on the formation of nitric oxide, superoxide, and nitrite peroxide may be responsible for the anti-inflammatory functionalities. Activated macrophage models could be used to identify the active components for functional diets development through a multiple targets strategy.

Keywords: cell model; epigenetic; peroxynitrite; tissue resident macrophages.

Figure 1

Multiple targets in macrophage attacked by nutraceuticals. FPT, farnesyl prenyl transferase; MG, methylglyoxal; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-coenzyme A; Farnesyl-PP, farnesyl pyrophosphate; F, farnesyl group; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositide 3-kinase; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; GR, glucocorticoid receptor; PPARγ, peroxisome proliferator-activated receptor gamma; AP1, activator protein 1; iNOS, inducible nitric oxide synthase; NO, nitric oxide; PKC, protein kinase C.