8.7
ValidityScore
Valid or Invalid?
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2012Human Cells
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Chen X, Chen YH, Huang YY, Liang YL, Song LH, Wang H, Xia MZ, Xu DX, Zhang C, Zhang ZH, Zhao M -
«Abstract: Increasing evidence demonstrates that melatonin has an anti-inflammatory effect. Nevertheless, the molecular mechanisms remain obscure. In this study, we investigated the effect of melatonin on toll-like receptor 4 (TLR4)-mediated molecule myeloid differentiation factor 88 (MyD88)-dependent and TRIF-dependent signaling pathways in lipopolysaccharide (LPS)-stimulated macrophages. RAW264.7 cell were incubated with LPS (2.0 μg/mL) in the absence or presence of melatonin (10, 100, 1000 μm). As expected, melatonin inhibited TLR4-mediated tumor necrosis factor alpha (TNF-α), interleukin IL-1β, IL-6, IL-8, and IL-10 in LPS-stimulated macrophages. In addition, melatonin significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in macrophages. Further analysis showed that melatonin inhibited the expression of MyD88 in LPS-stimulated macrophages. Although it had no effect on TLR4-mediated phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase (ERK), melatonin significantly attenuated the activation of nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. In addition, melatonin inhibited TLR4-mediated Akt phosphorylation in LPS-stimulated macrophages. Moreover, melatonin significantly attenuated the elevation of interferon (IFN)-regulated factor-3 (IRF3), which was involved in TLR4-mediated TRIF-dependent signaling pathway, in LPS-stimulated macrophages. Correspondingly, melatonin significantly alleviated LPS-induced IFN-β in macrophages. In conclusion, melatonin modulates TLR4-mediated inflammatory genes through MyD88-dependent and TRIF-dependent signaling pathways.»
- Dose: in the absence or presence of melatonin (10, 100, 1000 μm)
- Organism: In vitro
- Strong Magnitude of Effect.
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#Adaptor Proteins, Animals, Anti-Inflammatory Agents / pharmacology*, Cell Line, Cyclooxygenase 2 / genetics, Cyclooxygenase 2 / metabolism, Cytokines / genetics, Cytokines / metabolism, Dose-Response Relationship, Drug, Enzyme Activation, Gene Expression Regulation, Inflammation / genetics, Inflammation / immunology, Inflammation / metabolism, Inflammation / prevention &, Inflammation Mediators / metabolism*, Li-Hua Song, Lipopolysaccharides / pharmacology*, MEDLINE, Macrophages / drug effects*, Macrophages / immunology, Macrophages / metabolism, Melatonin / pharmacology*, Messenger / metabolism, Mi-Zhen Xia, Mice, Mitogen-Activated Protein Kinases / metabolism, Myeloid Differentiation Factor 88 / genetics, Myeloid Differentiation Factor 88 / metabolism*, NCBI, NF-kappa B / metabolism, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, Nitric Oxide Synthase Type II / genetics, Nitric Oxide Synthase Type II / metabolism, Non-U.S. Gov', Phosphorylation, Proto-Oncogene Proteins c-akt / metabolism, PubMed Abstract, RNA, Research Support, Signal Transduction / drug effects*, Time Factors, Toll-Like Receptor 4 / drug effects*, Toll-Like Receptor 4 / genetics, Toll-Like Receptor 4 / metabolism, Vesicular Transport / genetics, Vesicular Transport / metabolism*, Ying-Li Liang, control*, doi:10.1111/j.1600-079X.2012.01002.x, pmid:22537289more... -
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2012Rodents
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Chu P, Hsieh HY, Lin GJ, Lin SH, Lu KC, Sytwu HK, Wu CC -
« We checked the expression of proinflammatory cytokines (IL1b and tumor necrosis factor a [TNFa]), Th1 cytokines (IFN-γ and IL2), Th2 cytokines (IL4 and IL10), the fibrogenic cytokine transforming growth factor b (TGFb), and HO1. The expression of the proinflammatory cytokines, (IL1b, TNFa), Th1 cytokines, Th2 cytokines, and HO1 increased during MN (Fig. 5). The expression of the proinflammatory and Th1 cytokines in the MN-melatonin group was significantly lower than that in the control MN group (P < 0.05). In contrast, the expression of the Th2 cytokine IL4 was not affected by the melatonin treatment. We also found that although the expression of TGFb was not influenced by the melatonin treatment, the expression of IL10 was greatly increased in the MN-melatonin group (Fig. 5) compared with that in the MN group (P < 0.05). The melatonin treatment also dramatically induced HO1 expression in the spleen. These results demonstrate that melatonin treatment reduces proinflammatory cytokines and increases anti-inflammatory IL10, further suggesting that these immunomodulatory effects contribute to melatoninmediated protection against MN.»
- Dose: mice were immediately administered 20 mg/kg melatonin or phosphate-buffered saline subcutaneously once a day.
- Organism: Mouse / Rat (Rodents)
- Strong Magnitude of Effect.
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#Analysis of Variance, Animals, Antigens, Apoptosis / drug effects, Bovine, CD / biosynthesis, CD / immunology, Cattle, Chia-Chao Wu, Cytokines / genetics, Cytokines / metabolism, Female, Glomerulonephritis, Heme Oxygenase-1 / genetics, Heme Oxygenase-1 / metabolism*, Histocytochemistry, Huey-Kang Sytwu, Inbred BALB C, Kidney / chemistry, Kidney / drug effects, Kidney / pathology, Kuo-Cheng Lu, Lymphocytes / drug effects, Lymphocytes / immunology, MEDLINE, Melatonin / pharmacology*, Membranous / blood, Membranous / drug therapy*, Membranous / enzymology, Membranous / immunology*, Mice, NCBI, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, Non-U.S. Gov', Protective Agents / pharmacology, PubMed Abstract, Research Support, Serum Albumin, doi:10.1111/j.1600-079X.2011.00960.x, pmid:22288898more... -
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2011RCT
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De Teresa C, Díaz-Castro J, García C, Guisado IM, Guisado R, Kajarabille N, Ochoa JJ -
«The MG received an oral administration of five capsules of 3 mg of melatonin (Natrol, Chatsworth, CA, USA) supplied to each individual and used in the following manner: one capsule 2 days before the test with dinner, three capsules on the previous day (breakfast, lunch, and dinner), one capsule the same day of the run, 1 hr before beginning the physical test.»
«In addition to reducing oxidative stress parameters, melatonin significantly decreased the levels of proinflammatory cytokine TNF-α in the MG compared with the CG before the run (P < 0.001) (Fig. 2).»
«We also found a significant increase in the IL-6, after strenuous exercise in both groups (P < 0.001) (Fig. 2). Melatonin significantly decreased the levels of IL-6 in the MG compared with the CG before the run (P < 0.001) (Fig. 1). During exercise, IL-6 is produced by muscle fiber via a TNF-independent pathway.» - Dose: The MG received an oral administration of five capsules of 3 mg of melatonin (Natrol, Chatsworth, CA, USA) supplied to each individual and used in the following manner: one capsule 2 days before the test with dinner, three capsules on the previous day (breakfast, lunch, and dinner), one capsule the same day of the run, 1 hr before beginning the physical tes
- Organism: Humans
- Strong Magnitude of Effect.
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#-Deoxyguanosine, 8-Hydroxy-2', Controlled Clinical Trial, Deoxyguanosine / analogs &, Deoxyguanosine / urine, Dietary Supplements, Exercise / physiology*, Humans, Inflammation / blood, Inflammation / drug therapy*, Inflammation / etiology, Interleukin 1 Receptor Antagonist Protein / blood, Interleukin-6 / blood, Isoprostanes / urine, Javier Díaz-Castro, Julio J Ochoa, MEDLINE, Male, Melatonin / therapeutic use*, NCBI, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, Oxidative Stress / drug effects*, PubMed Abstract, Rafael Guisado, Tumor Necrosis Factor-alpha / blood, derivatives, doi:10.1111/j.1600-079X.2011.00899.x, pmid:21615492more... -
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2009Rodents
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Jiang YX, Shang Y, Wu Y, Wu ZY, Xu SP, Yao SL, Yuan SY -
«PaO(2) in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1 +/- 0.18) as compared with that in the vehicle + saline group (3.61 +/- 0.3) (P < 0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8 +/- 0.25) (P < 0.01). Myeloperoxidase activity and malondialdehyde (MDA) levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which was reduced in the melatonin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the vehicle + lipopolysaccharide group ((8.7 +/- 0.91) pg/mg protein) compared with that in the vehicle + saline group ((4.3 +/- 0.62) pg/mg protein, P < 0.01). However, the increase of TNF-alpha (TNF-α) level of pulmonary tissue was significantly reduced in the melatonin + lipopolysaccharide group ((5.9 +/- 0.56) pg/mg protein, P < 0.01). Pulmonary IL-10 levels were elevated markedly in the vehicle + lipopolysaccharide group in contrast to that in the vehicle + saline group, whereas the elevation was augmented in the melatonin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin + lipopolysaccharide group.»
- Dose: The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (i.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection).
- Organism: Mouse / Rat (Rodents)
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#Acute Lung Injury / drug therapy, Acute Lung Injury / pathology*, Animals, Blotting, Endotoxemia / drug therapy, Endotoxemia / physiopathology*, Interleukin-10 / metabolism, Lipopolysaccharides / toxicity, Lung / drug effects*, Lung / metabolism, MEDLINE, Male, Melatonin / pharmacology*, NCBI, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, PubMed Abstract, Random Allocation, Rats, San-Peng Xu, Shang-Long Yao, Sprague-Dawley, Tumor Necrosis Factor-alpha / metabolism, Western, You Shang, pmid:19567158more... -
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2004RCT
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Barberi I, Calabrò MP, Chiurazzi P, Cordaro SP, Gitto E, Gitto P, La Rosa M, Reiter RJ, Trimarchi G -
«Abstract: Reactive oxygen species play an important role in the pathogenesis of respiratory distress syndrome and its complications. This study was conducted to determine if treatment with the antioxidant melatonin would influence interleukin-6, interleukin-8, tumor necrosis factor alpha (TNF-α), and nitrite/nitrate levels in newborns with grade III or IV respiratory distress syndrome (radiographically confirmed) diagnosed within the first 6 hours of life. Prior to treatment, a blood sample was collected from the umbilical cord or a peripheral vein of each newborn. Second, third, and fourth blood samples were collected at 24 hours, 72 hours, and 7 days, respectively, after beginning treatment with melatonin or placebo. Compared with the melatonin-treated respiratory distress syndrome newborns, in the untreated infants the concentration of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha were significantly higher at 24 hours, 72 hours, and at 7 days after onset of the study. in addition, nitrite/nitrate levels at all time points were higher in the untreated respiratory distress syndrome newborns than in the melatonin-treated babies. Following melatonin administration, nitrite/nitrate levels decreased significantly, whereas they remained high and increased further in the respiratory distress syndrome infants not given melatonin.»
- Organism: Humans
- Strong Magnitude of Effect.
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#Antioxidants / pharmacology, Antioxidants / therapeutic use*, Clinical Trial, Controlled Clinical Trial, Eloisa Gitto, Humans, Ignazio Barberi, Infant, Interleukin-6 / blood, Interleukin-8 / blood, MEDLINE, Melatonin / pharmacology, Melatonin / therapeutic use*, NCBI, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, Newborn, Newborn / drug therapy*, Newborn / immunology, Nitrates / blood, Nitrites / blood, Non-U.S. Gov', Nonparametric, Oxidative Stress / drug effects*, Premature / blood*, PubMed Abstract, Research Support, Respiratory Distress Syndrome, Russel J Reiter, Statistics, Time Factors, Treatment Outcome, Tumor Necrosis Factor-alpha / metabolism, doi:10.1055/s-2004-828610, pmid:15168319more... -
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on Oct 15, 2021