Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms.

In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress-induced GC resistance in human macrophage-like cells. Cells were pre-treated with H2O2 (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2',7'-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect.

The cocoa flavanol (-)-epicatechin protects the cortisol response.

Various health benefits of the cocoa flavanol (-)-epicatechin (EC) have been attributed to its antioxidant and anti-inflammatory potency. In the present study we investigated whether EC is able to prevent deterioration of the anti-inflammatory effect of the glucocorticoid (GC) cortisol in the presence of oxidative stress. It was found that cortisol reduces inflammation in differentiated monocytes. Oxidative stress extinguishes the anti-inflammatory effect of cortisol, leading to cortisol resistance. EC reduces intracellular oxidative stress as well as the development of cortisol resistance. This further deciphers the enigmatic mechanism of EC by which it exerts its anti-inflammatory and antioxidant action. The observed effect of the cocoa flavanol EC will especially be of relevance in pathophysiological conditions with increased oxidative stress and consequential GC resistance and provides a fundament for the rational use of dietary antioxidants.

Epigenetics: prenatal exposure to genistein leaves a permanent signature on the hematopoietic lineage.

Recent studies demonstrate that maternal diet during pregnancy results in long-lasting effects on the progeny. Supplementation of maternal diet with genistein, a phytoestrogen ubiquitous in the daily diet, altered coat color of agouti mice due to epigenetic changes. We studied hematopoiesis of mice prenatally exposed to genistein (270 mg/kg feed) compared with that of mice prenatally exposed to phytoestrogen-poor feed and observed a significant increase in granulopoiesis, erythropoiesis, and mild macrocytosis at the adult age of 12 wk. Genistein exposure was associated with hypermethylation of certain repetitive elements, which coincided with a significant down-regulation of estrogen-responsive genes and genes involved in hematopoiesis in bone marrow cells of genistein-exposed mice, as assessed by microarray technology. Although genistein exposure did not affect global methylation in fetal liver of fetuses at embryonic day 14.5, it accelerated the switch from primitive to definitive erythroid lineage. Taken together, our data demonstrate that prenatal exposure to genistein affects fetal erythropoiesis and exerts lifelong alterations in gene expression and DNA methylation of hematopoietic cells.