Coffee and Maillard products activate NF-jB\ud in macrophages via H2O2 production

In this study, we investigated the immunomodulatory activity of coffee and Maillard reaction products on macrophages in vitro. Stimulation of macrophages with coffee, but not with raw coffee extract in PBS, led to a 13-fold increased nuclear NF-B translocation. A Maillard reaction mixture (25 mM D-ribose/L-lysine, 30 min at 120°C) increased NF-B translocation 18-fold (in PBS) or six-fold (in medium). MRPs also induced a two-fold increased NF-B translocation in untransfected human embryonic kidney (HEK) cells as well as in HEK cells stably transfected with the receptor for advanced glycation endproducts (RAGE), indicating that the effect was not RAGE mediated. On the other hand, catalase totally abolished coffee- and MRP-induced NF-B translocation. Consequently, up to 366 M hydrogen peroxide was measured in the coffee preparation and Maillard mixtures used for cell stimulation. Stimulation of macrophages with MRPs did not lead to significantly increased IL-6 or NO release. Thus, it can be concluded that coffee and MRPs induce NF-B translocation in macrophages via the generation of hydrogen peroxide

Nuclear translocation of NF-ϰB in intact human gut tissue upon stimulation with coffee and roasting products

In the healthy gut, NF-ϰB is a critical factor of the intestinal immune system, whereas inflammatory bowel diseases are associated with chronic activation of NF-ϰB. Previous studies indicated that coffee induces nuclear translocation of NF-ϰB in macrophages, an effect attributed to roasting products. In the present work, coffee extract or roasting products induced nuclear translocation of NF-ϰB in macrophages, Caco-2 cells, and primary human intestinal microvascular endothelial cells (up to fivefold, p ˂ 0.001). Since the effect clearly depended on the cell type, ex vivo experiments were performed with intact human gut tissue from biopsies. The uniformity of the specimens and tissue viability during ex vivo incubation for up to 2 h were verified. Roasting products led to a concentration dependent significant increase of nuclear translocation of NF-ϰB in human gut tissue (up to 2.85 fold increase, p = 0.0321), whereas coffee extract induced a trend towards higher nuclear NF-ϰB concentration. NF-ϰB activation in macrophages and Caco-2 cells by roasting products was significantly blocked by co-incubation with catalase (p = 0.011 and p = 0.024) indicating involvement of H2O2-signaling. Monitoring of extracellular H2O2 indicated that roasting products in coffee constantly generate H2O2 by spontaneous oxygen reduction, which is only partially detoxified by cellular antioxidative systems. Thus, it can be concluded that ex vivo stimulation of intact human gut tissue is a valuable model to study nutritional effects on complex tissue systems. Furthermore, the consumption of coffee and roasting products may be able to induce nuclear NF-ϰB translocation in the human gut

Lipoic acid as a novel treatment for Alzheimer's disease and related dementias

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that destroys patient memory and cognition, communication ability with the social environment and the ability to carry out daily activities. Despite extensive research into the pathogenesis of AD, a neuroprotective treatment – particularly for the early stages of disease – remains unavailable for clinical use. In this review, we advance the suggestion that lipoic acid (LA) may fulfil this therapeutic need. A naturally occurring precursor of an essential cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH), LA has been shown to have a variety of properties which can interfere with pathogenic principles of AD. For example, LA increases acetylcholine (ACh) production by activation of choline acetyltransferase and increases glucose uptake, thus supplying more acetyl-CoA for the production of ACh. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals and also scavenges reactive oxygen species (ROS), thereby increasing the levels of reduced glutathione. Via the same mechanisms, downregulation redox-sensitive inflammatory processes is also achieved. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. The reduced form of LA, dihydrolipoic acid (DHLA), is the active compound responsible for most of these beneficial effects. R-α-LA can be applied instead of DHLA, as it is reduced by mitochondrial lipoamide dehydrogenase, a part of the PDH complex. In this review, the properties of LA are explored with particular emphasis on how this agent, particularly the R-α-enantiomer, may be effective to treat AD and related dementias