Possible Involvement of the Inhibition of NF-κB Factor in Anti-Inflammatory Actions That Melatonin Exerts on Mast Cells.

Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc.

Melatonin protects mast cells against cytotoxicity mediated by chemical stimuli PMACI: possible clinical use.

Melatonin has documented cytoprotective effects on a wide variety of immune cells. The mechanism of action on mast cells (RBL-2H3) still remains in the dark. We found that melatonin significantly attenuated phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced cytotoxicity in a concentration and time-dependent manner. It appears that the effect of melatonin on mast cells is two-fold: dependent (MT1 and MT2) and independent membrane receptors. In conclusion, melatonin treatment reduced the cytotoxicity, mediated by PMACI, and could provide a useful therapeutic option in processes where an excessive activation of mast cells occurs.

High levels of melatonin generated during the brewing process.

Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin.

Melatonin administrated immediately before an intense exercise reverses oxidative stress, improves immunological defenses and lipid metabolism in football players.

Acute sport exercise leads to a strong stimulation of muscle tissue and a change in the organism energy demands. This study was designed to investigate the effect of oral melatonin supplementation on human physiological functions associated with acute exercise. Immune, endocrine and metabolic parameters were measured in 16 young male football players, who were divided into two groups, an experimental group (supplementation with 6 mg of melatonin administered 30 min prior to exercise) and a control group (placebo without melatonin). They performed a continuous exercise of high intensity (135 beats/min). Samples were collected 30 min before the exercise and 3, 15 and 60 min during the exercise. The results indicated that the acute sport training presented: a) increased lipid peroxidation products (MDA) in both groups, control and experimental, with levels significantly decreased in the group treated with melatonin after 15 and 60 min of high-intensity exercise, b) the total antioxidant activity (TAS) was lower in the control group than in the experimental, the latter showing significant differences at 60 min of high-intensity exercise c) the lipid profile of subjects in the experimental group showed lower triglyceride levels than the control group after 15 and 60 min of high-intensity exercise, d) immunological studies only showed, in the experimental group, an increase in IgA levels at 60 min after the exercise, and finally there were no significant differences between the groups for any of the other variables. In conclusion these results indicated that treatment with melatonin in acute sports exercise reversed oxidative stress, improved defenses and lipid metabolism, which would result in an improvement in fitness.