{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:56:35Z","timestamp":1781920595529,"version":"3.54.5"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The recent pandemic of COVID-19 has already infected millions of individuals and has resulted in the death of hundreds of thousands worldwide. Based on clinical features, pathology, and the pathogenesis of respiratory disorders induced by this and other highly homogenous coronaviruses, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response contribute to COVID-19 pathology; these are caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This leads to a cytokine storm and subsequent progression triggering acute lung injury (ALI)\/acute respiratory distress syndrome (ARDS), and often death. We and others have reported melatonin to be an anti-inflammatory and anti-oxidative molecule with a high safety profile. It is effective in critical care patients by reducing their vascular permeability and anxiety, inducing sedation, and improving their quality of sleep. As melatonin shows no harmful adverse effects in humans, it is imperative to introduce this indoleamine into clinical trials where it might be beneficial for better clinical outcomes as an adjuvant treatment of COVID-19-infected patients. Herein, we strongly encourage health care professionals to test the potential of melatonin for targeting the COVID-19 pandemic. This is urgent, since there is no reliable treatment for this devastating disease.<\/jats:p>","DOI":"10.3390\/nu12092561","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T10:37:32Z","timestamp":1598265452000},"page":"2561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Clinical Trials for Use of Melatonin to Fight against COVID-19 Are Urgently Needed"],"prefix":"10.3390","volume":"12","author":[{"given":"Konrad","family":"Kleszczy\u0144ski","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, Von-Esmarch-Str. 58, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8963-3995","authenticated-orcid":false,"given":"Andrzej T.","family":"Slominski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Pathology and Laboratory Medicine Service, VA Medical Center, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Steinbrink","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of M\u00fcnster, Von-Esmarch-Str. 58, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology, UT Health, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"ref_1","unstructured":"European Centre for Disease Prevention and Control (2020, July 22). COVID-19 Situation Update Worldwide, as of 20 July 2020. Available online: https:\/\/www.ecdc.europa.eu\/en\/geographical-distribution-2019-ncov-cases."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/jmv.25685","article-title":"Coronavirus infections and immune responses","volume":"92","author":"Li","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1600-079X.2012.01028.x","article-title":"Melatonin prevents ultraviolet radiation-induced alterations in plasma membrane potential and intracellular pH in human keratinocytes","volume":"54","author":"Tukaj","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hardeland, R. (2019). Aging, melatonin, and the pro- and anti-inflammatory networks. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051223"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12525","DOI":"10.1111\/jpi.12525","article-title":"Melatonin and inflammation-story of a double-edged blade","volume":"65","author":"Hardeland","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117191","DOI":"10.1016\/j.lfs.2019.117191","article-title":"Effect of melatonin on T\/B cell activation and immune regulation in pinealectomy mice","volume":"242","author":"Luo","year":"2020","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"297","DOI":"10.32794\/mr11250063","article-title":"Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): A case series","volume":"3","author":"Castillo","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zeng, Z., Xu, L., Xie, X.Y., Yan, H.L., Xie, B.J., Xu, W.Z., Liu, X.A., Kang, G.J., Jiang, W.L., and Yuan, J.P. (2020). Pulmonary pathology of early phase COVID-19 pneumonia in a patient with a benign lung lesion. Histopathology.","DOI":"10.1111\/his.14138"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological findings of COVID-19 associated with acute respiratory distress syndrome","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/jmv.25709","article-title":"Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV","volume":"92","author":"Liu","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117583","DOI":"10.1016\/j.lfs.2020.117583","article-title":"COVID-19: Melatonin as a potential adjuvant treatment","volume":"250","author":"Zhang","year":"2020","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.chom.2016.01.007","article-title":"Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice","volume":"19","author":"Channappanavar","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Smits, S.L., de Lang, A., van den Brand, J.M.A., Leijten, L.M., van IJcken, W.F., Eijkemans, M.J.C., van Amerongen, G., Kuiken, T., Andeweg, A.C., and Osterhaus, A.D.M.E. (2010). Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000756"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2109","DOI":"10.1002\/rmv.2109","article-title":"Melatonin: Roles in influenza, Covid-19, and other viral infections","volume":"30","author":"Anderson","year":"2020","journal-title":"Rev. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/rmv.1714","article-title":"Beneficial actions of melatonin in the management of viral infections: A new use for this \u201cmolecular handyman\u201d?","volume":"22","author":"Boga","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/jpi.12338","article-title":"Melatonin enhances mitochondrial ATP synthesis, reduces reactive oxygen species formation, and mediates translocation of the nuclear erythroid 2-related factor 2 resulting in activation of phase-2 antioxidant enzymes (\u03b3-GCS, HO-1, NQO1) in ultraviolet radiation-treated normal human epidermal keratinocytes (NHEK)","volume":"61","author":"Zillikens","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/jpi.12197","article-title":"Melatonin compensates silencing of heat shock protein 70 and suppresses ultraviolet radiation-induced inflammation in human skin ex vivo and cultured keratinocytes","volume":"58","author":"Zwicker","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jid.2017.10.025","article-title":"Melatonin: A cutaneous perspective on its production, metabolism, and functions","volume":"138","author":"Slominski","year":"2018","journal-title":"J. Invest. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12560","DOI":"10.1111\/jpi.12560","article-title":"Melatonin attenuates TNF-\u03b1 and IL-1\u03b2 expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis","volume":"66","author":"Huang","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lfs.2018.08.037","article-title":"MicroRNA-494 inhibition alleviates acute lung injury through Nrf2 signaling pathway via NQO1 in sepsis-associated acute respiratory distress syndrome","volume":"210","author":"Ling","year":"2018","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.0902961","article-title":"Melatonin protects CD4+ T cells from activation-induced cell death by blocking NFAT-mediated CD95 ligand upregulation","volume":"184","author":"Pedrosa","year":"2010","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1111\/jpi.12199","article-title":"Systemic combined melatonin-mitochondria treatment improves acute respiratory distress syndrome in the rat","volume":"58","author":"Sun","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2174\/1568026616666160824120338","article-title":"Melatonin and respiratory diseases: A review","volume":"17","author":"Habtemariam","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_28","first-page":"57","article-title":"Melatonin: A potent, endogenous hydroxyl radical scavenger","volume":"1","author":"Tan","year":"1993","journal-title":"Endocr. J."},{"key":"ref_29","first-page":"103","article-title":"Antioxidant capacity of melatonin: A novel action not requiring a receptor","volume":"15","author":"Reiter","year":"1993","journal-title":"Neuroendocrinol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"181","DOI":"10.2174\/1568026023394443","article-title":"Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger","volume":"2","author":"Tan","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1007\/s00018-017-2610-1","article-title":"Melatonin, clock genes and mitochondria in sepsis","volume":"74","author":"Rahim","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3883","DOI":"10.1007\/s00018-017-2615-9","article-title":"Melatonin and the electron transport chain","volume":"74","author":"Hardeland","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s00018-017-2609-7","article-title":"Melatonin as a mitochondria-targeted antioxidant: One of evolution\u2019s best ideas","volume":"74","author":"Reiter","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J., and Xu, B. (2018). Mitochondria: Central organelles for melatonin\u2019s antioxidant and anti-aging actions. Molecules, 23.","DOI":"10.3390\/molecules23020509"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tan, D.X., Manchester, L.C., Qin, L., and Reiter, R.J. (2016). Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122124"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1007\/s00018-017-2614-x","article-title":"Melatonin as a mitochondrial protector in neurodegenerative diseases","volume":"74","author":"Wongprayoon","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"L820","DOI":"10.1152\/ajplung.90211.2008","article-title":"Effects of melatonin in an experimental model of ventilator-induced lung injury","volume":"295","author":"Pedreira","year":"2008","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12931-020-1325-2","article-title":"Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production","volume":"21","author":"Wu","year":"2020","journal-title":"Respir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/10715760290032593","article-title":"Effects of antioxidants on surfactant peroxidation by stimulated human polymorphonuclear leukocytes","volume":"36","author":"Bouhafs","year":"2002","journal-title":"Free Radic. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1600-079X.1999.tb00570.x","article-title":"Interactions of melatonin with membrane models: Portioning of melatonin in AOT and lecithin reversed micelles","volume":"26","author":"Ceraulo","year":"1999","journal-title":"J. Pineal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"120","DOI":"10.32794\/mr11250052","article-title":"Potential utility of melatonin in deadly infectious diseases related to the overreaction of innate immune response and destructive inflammation: Focus on COVID-19","volume":"3","author":"Tan","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.32794\/mr11250047","article-title":"Treatment of Ebola and other infectious diseases: Melatonin \u201cgoes viral\u201d","volume":"3","author":"Reiter","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_43","first-page":"439","article-title":"Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury","volume":"6","author":"Chen","year":"2014","journal-title":"Am. J. Transl. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/icvts\/ivx440","article-title":"Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of oxidative stress and inflammation","volume":"26","author":"Wang","year":"2018","journal-title":"Interact. Cardiov. Thorac. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/cphy.c100068","article-title":"Oxidants and redox signaling in acute lung injury","volume":"1","author":"Sarma","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1055\/s-2004-828610","article-title":"Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: Beneficial effects of melatonin","volume":"21","author":"Gitto","year":"2004","journal-title":"Am. J. Perinatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/j.1600-079X.2005.00251.x","article-title":"Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: Improvement with melatonin treatment","volume":"39","author":"Gitto","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev-virology-092917-043515","article-title":"Quis Custodiet Ipsos Custodes? Regulation of cell mediated immune responses following viral lung infections","volume":"5","author":"Rogers","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1385\/ENDO:27:2:101","article-title":"Functional MT1 and MT2 melatonin receptors in mammals","volume":"27","author":"Dubocovich","year":"2005","journal-title":"Endocrine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0165-5728(86)90047-0","article-title":"Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone","volume":"13","author":"Maestroni","year":"1986","journal-title":"J. Neuroimmunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2174\/1568026023394335","article-title":"Melatonin-Immune system relationships","volume":"2","author":"Guerrero","year":"2002","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/13543784.10.3.467","article-title":"The immunotherapeutic potential of melatonin","volume":"10","author":"Maestroni","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/s11427-020-1643-8","article-title":"Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury","volume":"63","author":"Liu","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.0959-9673.2006.00474.x","article-title":"The role of melatonin in immuno-enhancement: Potential application in cancer","volume":"87","author":"Miller","year":"2006","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.3389\/fphar.2019.01600","article-title":"Rhein suppresses lung inflammatory injury induced by human respiratory syncytial virus through inhibiting NLRP3 inflammasome activation via NF-\u03baB pathway in mice","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27912","DOI":"10.1038\/srep27912","article-title":"Reassessing the role of the NLRP3 inflammasome during pathogenic influenza a virus infection via temporal inhibition","volume":"6","author":"Tate","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_57","first-page":"4087298","article-title":"Melatonin alleviates radiation-induced lung injury via regulation of miR-30e\/NLRP3 axis","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxidat. Med. Cell. Longev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"117067","DOI":"10.1016\/j.lfs.2019.117067","article-title":"Melatonin biosynthesis restored by CpG oligodeoxynucleotides attenuates allergic airway inflammation via regulating NLRP3 inflammasome","volume":"239","author":"Wu","year":"2019","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/jpi.12322","article-title":"Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome","volume":"60","author":"Zhang","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_60","first-page":"945","article-title":"Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1alpha\/ROS\/VEGF","volume":"43","author":"Cheng","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109150","DOI":"10.1016\/j.biopha.2019.109150","article-title":"Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1\/STAT3 pathway","volume":"117","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1002\/jcp.29190","article-title":"Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: A new mechanism involving BAP31 upregulation and MAPK-ERK pathway","volume":"235","author":"Zhang","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/jpi.12286","article-title":"Role of toll-like receptor 4 in melatonin-induced cardioprotection","volume":"60","author":"Nduhirabandi","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2174\/1570159X14666161228122115","article-title":"Melatonin: Pharmacology, functions and therapeutic benefits","volume":"15","author":"Tordjman","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_65","first-page":"CD012455","article-title":"Melatonin for the promotion of sleep in adults in the intensive care unit","volume":"5","author":"Lewis","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.sleep.2020.01.019","article-title":"The role of melatonin and melatonin receptor agonist in the prevention of sleep disturbances and delirium in intensive care unit\u2014A clinical review","volume":"69","author":"Lewandowska","year":"2020","journal-title":"Sleep Med."},{"key":"ref_67","first-page":"1298","article-title":"Melatonin reduces the need for sedation in ICU patients: A randomized controlled trial","volume":"81","author":"Mistraletti","year":"2015","journal-title":"Minerva Anestesiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1080\/09537104.2020.1760230","article-title":"Prediction of severe illness due to COVID-19 based on an analysis of initial fibrinogen to albumin ratio and platelet count","volume":"31","author":"Bi","year":"2020","journal-title":"Platelets"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/jpi.12186","article-title":"Ebola virus disease: Potential use of melatonin as a treatment","volume":"57","author":"Tan","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/jpi.12134","article-title":"Melatonin as a potential therapy for sepsis: A phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis","volume":"56","author":"Galley","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2009.00728.x","article-title":"Malaria: Therapeutic implications of melatonin","volume":"48","author":"Srinivasan","year":"2010","journal-title":"J. Pineal Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1001\/archophthalmol.2010.321","article-title":"Retinal toxicity associated with hydroxychloroquine and chloroquine","volume":"129","author":"Michaelides","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_73","first-page":"77","article-title":"Comparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury","volume":"93","author":"Kaptanoglu","year":"2000","journal-title":"J. Neurosur."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1007\/s00586-003-0550-y","article-title":"Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury","volume":"13","author":"Cayli","year":"2004","journal-title":"Eur. Spine J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jff.2019.04.062","article-title":"Melatonin possesses an anti-influenza potential through its immune modulatory effect","volume":"58","author":"Huang","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.pneurobio.2010.12.004","article-title":"Melatonin \u2014A pleiotropic, orchestrating regulator molecule","volume":"93","author":"Hardeland","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2011.08.025","article-title":"Melatonin: The smart killer: The human trophoblast as a model","volume":"348","author":"Lanoix","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7396","DOI":"10.3390\/molecules20047396","article-title":"Phytomelatonin: Assisting plants to survive and thrive","volume":"20","author":"Reiter","year":"2015","journal-title":"Molecules"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tem.2007.10.007","article-title":"Melatonin in the skin: Synthesis, metabolism and functions","volume":"19","author":"Slominski","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.arcmed.2018.12.004","article-title":"Efficacy of melatonin on serum pro-inflammatory cytokines and oxidative stress markers in relapsing remitting multiple sclerosis","volume":"49","author":"Ortiz","year":"2018","journal-title":"Arch. Med. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e12521","DOI":"10.1111\/jpi.12521","article-title":"The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In Vivo assessment and a randomized controlled trial","volume":"65","author":"Zhao","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e11383","DOI":"10.1097\/MD.0000000000011383","article-title":"Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial","volume":"97","author":"Shafiei","year":"2018","journal-title":"Medicine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1210\/jcem-45-4-768","article-title":"The effects of oral melatonin on skin color and on the release of pituitary hormones","volume":"45","author":"Nordlund","year":"1977","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1600-079X.2006.00377.x","article-title":"Reduced oxidative damage in ALS by high-dose enteral melatonin treatment","volume":"41","author":"Weishaupt","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1600-079X.2011.00854.x","article-title":"The use of high-dose melatonin in liver resection is safe: First clinical experience","volume":"50","author":"Nickkholgh","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ctim.2018.06.002","article-title":"Use of melatonin as adjunctive therapy in neonatal sepsis: A systematic review and meta-analysis","volume":"39","author":"Henderson","year":"2018","journal-title":"Complement. Ther. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1080\/14767058.2017.1342794","article-title":"Beneficial effect of melatonin in the treatment of neonatal sepsis","volume":"31","author":"Hassan","year":"2018","journal-title":"J. Matern. Fetal. Neonatal. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/exd.13208","article-title":"Metabolism of melatonin in the skin: Why is it important?","volume":"26","author":"Slominski","year":"2017","journal-title":"Exp. Dermatol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/9\/2561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:50Z","timestamp":1760177150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/9\/2561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,24]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["nu12092561"],"URL":"https:\/\/doi.org\/10.3390\/nu12092561","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,24]]}}}