title: Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, Maastricht 3600 MD, The Netherlands. erik_ruijters@hotmail.com.
authors.forename: Erik J B
authors.initials: EJ
authors.lastname: Ruijters
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, Maastricht 3600 MD, The Netherlands. g.haenen@maastrichtuniversity.nl.
authors.forename: Guido R M M
authors.initials: GR
authors.lastname: Haenen
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, Maastricht 3600 MD, The Netherlands. mathijs.willemsen@mumc.nl.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Willemsen
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, Maastricht 3600 MD, The Netherlands. a.weseler@maastrichtuniversity.nl.
authors.forename: Antje R
authors.initials: AR
authors.lastname: Weseler
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health, Medicine and Health Sciences, Maastricht University, Maastricht 3600 MD, The Netherlands. a.bast@maastrichtuniversity.nl.
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D004351:Drug Resistance / Q000187:drug effects; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005419:Flavonoids; D017382:Reactive Oxygen Species; D006854:Hydrocortisone
keywords: antioxidant; cortisol; flavonoids; glucocorticoid; inflammation