Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease

Chitimus, Diana Maria; Popescu, Mihaela Roxana; Voiculescu, Suzana Elena; Panaitescu, Anca Maria; Pavel, Bogdan; Zagrean, Leon; Zagrean, Ana-Maria

doi:10.3390/biom10091211

Cited by 354Circadian rhythm and melatoninAntioxidant Activity and Oxidative Stressmelanin and skin pigmentation

Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease

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Chitimus, Diana Maria, Popescu, Mihaela Roxana, Voiculescu, Suzana Elena, Panaitescu, Anca Maria, Pavel, Bogdan, Zagrean, Leon, Zagrean, Ana-Maria·2020·Biomolecules

DOI 10.3390/biom10091211PMC PMC7563541

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Abstract

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

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Melatonin interferes with inflammatory processes by interacting with cyclooxygenase (COX2), which is a key mediator of inflammatory processes and promotes apoptosis in malignant cells.
“Melatonin interferes with inflammatory processes by interacting with cyclooxygenase (COX2), which is a key mediator of inflammatory processes and promotes apoptosis in malignant cells (Favero et al. 2017; Chitimus et al. 2020).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Chitimus et al. 2020
Melatonin's dual actions can inhibit pro-oxidative enzymes (e.g., xanthine oxidase) while also potentiating critical antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase, and catalase.
“Melatonin’s dual actions can inhibit pro-oxidative enzymes (e.g., xanthine oxidase) while also acting to potentiate the critical antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase, and catalase, aiding in the body’s first line of immune defense and metabolic detoxification [31,32].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
Low levels of melatonin may trigger an upregulation in the kynurenine pathway, and kynurenine production, as well as trigger the aryl hydrocarbon receptor (AhR) located on the outer membrane of the mitochondria.
“Low levels of melatonin may trigger an upregulation in the kynurenine pathway, and kynurenine production, as well as trigger the aryl hydrocarbon receptor (AhR) located on the outer membrane of the mitochondria [32,55,56,57,58].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
Acute or chronic inflammation and stress have been found to increase the throughput of the kynurenine pathway, leading to an increase in tryptophan's conversion to kynurenine.
“Conversely, acute or chronic inflammation and stress have been found to increase the throughput of the kynurenine pathway, leading to an increase in tryptophan’s conversion to kynurenine [32,55].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
When AhR is triggered, overall endogenous pineal melatonin production is suppressed.
“When AhR is triggered, overall endogenous pineal melatonin production is suppressed [32,55,56,57,58].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]

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Melatonin alleviates vascular calcification and ageing through exosomal miR‐204/miR‐211 cluster in a paracrine manner
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Chronic melatonin consumption prevents obesity‐related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet‐induced obesity
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Insomnia with physiological hyperarousal is associated with hypertension
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Blood-Brain Barrier Disruption Induced by Chronic Sleep Loss: Low-Grade Inflammation May Be the Link
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Melatonin increases cleavage rate of porcine preimplantation embryos in vitro
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Protective effects of melatonin in ischemic brain injury
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Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies
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The circadian melatonin rhythm and its modulation: possible impact on hypertension
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Decreased nocturnal melatonin levels during acute myocardial infarction
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Role of melatonin in embryo fetal development.
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Melatonin reduces cardiac inflammatory injury induced by acute exercise
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Inhibitors of Cytochrome c Release with Therapeutic Potential for Huntington's Disease
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Melatonin effects on myocardial ischemia–reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery
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Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release
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Melatonin: the dawning of a treatment for fibrosis?
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Melatonin ameliorates vascular endothelial dysfunction, inflammation, and atherosclerosis by suppressing the TLR 4/ NF ‐κB system in high‐fat‐fed rabbits
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Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease
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Role of melatonin in blood pressure regulation: An adjunct anti‐hypertensive agent
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Melatonin receptors in human fetal brain: 2‐[125I]iodomelatonin binding and MT1 gene expression
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Type 2 diabetes mellitus: Role of melatonin and oxidative stress
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Measuring Light at Night and Melatonin Levels in Shift Workers: A Review of the Literature
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Shift work, duration of pregnancy, and birth weight:
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Urinary 6‐sulfatoxymelatonin levels and their correlations with lifestyle factors and steroid hormone levels
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The protective effect of melatonin on brain ischemia and reperfusion in rats and humans: In vivo assessment and a randomized controlled trial
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Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain
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Melatonin Scavenger Properties against Oxidative and Nitrosative Stress: Impact on Gamete Handling and In Vitro Embryo Production in Humans and Other Mammals
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Melatonin attenuates kainic acid‐induced neurotoxicity in mouse hippocampus via inhibition of autophagy and α‐synuclein aggregation
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Preeclampsia and Pregnancy-Related Hypertensive Disorders
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Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury
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Melatonin attenuates amyloid beta25–35-induced apoptosis in mouse microglial BV2 cells
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A Double-Blind, Placebo-Controlled Trial Related to the Effects of Melatonin on Oxidative Stress and Inflammatory Parameters of Obese Women
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Melatonin has multiorgan effects
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Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis
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Melatonin transport into mitochondria
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Cardiovascular Benefits of Dietary Melatonin: A Myth or a Reality?
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Apolipoprotein E Deficiency Aggravates Neuronal Injury by Enhancing Neuroinflammation via the JNK/c-Jun Pathway in the Early Phase of Experimental Subarachnoid Hemorrhage in Mice
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Acute dose of melatonin via Nrf2 dependently prevents acute ethanol-induced neurotoxicity in the developing rodent brain
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Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double‐blind, placebo‐controlled study
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Update on the use of melatonin in pediatrics
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Light and Circadian Signaling Pathway in Pregnancy: Programming of Adult Health and Disease
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Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST ‐elevation myocardial infarction: Results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial
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Usefulness of Early Treatment With Melatonin to Reduce Infarct Size in Patients With ST-Segment Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention (From the Melatonin Adjunct in the Acute Myocardial Infarction Treated With Angioplasty Trial)
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Melatonin Reduces Oxidative Stress Damage Induced by Hydrogen Peroxide in Saccharomyces cerevisiae
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N -Acetylserotonin and 6-Hydroxymelatonin against Oxidative Stress: Implications for the Overall Protection Exerted by Melatonin
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Pharmacokinetics of Alternative Administration Routes of Melatonin: A Systematic Review
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Protective role of melatonin in mitochondrial dysfunction and related disorders
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Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction
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Light at night and melatonin have opposite effects on breast cancer tumors in mice assessed by growth rates and global DNA methylation
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Melatonin promotes secondary hair follicle development of early postnatal cashmere goat and improves cashmere quantity and quality by enhancing antioxidant capacity and suppressing apoptosis
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Melatonin as a preventive and curative therapy against pulmonary hypertension
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Programming of the fetal suprachiasmatic nucleus and subsequent adult rhythmicity
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Melatonin Concentrations and Antioxidative Capacity of Human Breast Milk According to Gestational Age and the Time of Day
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MT3 melatonin binding site, MT1 and MT2 melatonin receptors are present in oocyte, but only MT1 is present in bovine blastocyst produced in vitro
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Beneficial effects of melatonin in a rat model of sporadic Alzheimer’s disease
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Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction
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Effectiveness of Melatonin for the Prevention of Intensive Care Unit Delirium
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Developmental Programming of Adult Disease: Reprogramming by Melatonin?
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Melatonin protects against behavioral deficits, dopamine loss and oxidative stress in homocysteine model of Parkinson's disease
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Melatonin protects primary cultures of rat cortical neurones from NMDA excitotoxicity and hypoxia/reoxygenation
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Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in Treating Pulmonary Hypertension with Melatonin
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Getting an Early Start in Understanding Perinatal Asphyxia Impact on the Cardiovascular System
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Impaired nocturnal synthesis of melatonin in patients with cardiac syndrome X.
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Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol
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Dual Effect of Catecholamines and Corticosterone Crosstalk on Pineal Gland Melatonin Synthesis
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Protective roles of melatonin in central nervous system diseases by regulation of neural stem cells
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Peroxynitrite in the Pathogenesis of Parkinson's Disease and the Neuroprotective Role of Metallothioneins
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Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis
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Preventive effect of melatonin on bleomycin‐induced lung fibrosis in rats
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Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson’s disease. An integrated strategy for management
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Melatonin improves mitochondrial biogenesis through the AMPK/PGC1α pathway to attenuate ischemia/reperfusion-induced myocardial damage
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Melatonin Attenuates Calcium Deposition from Vascular Smooth Muscle Cells by Activating Mitochondrial Fusion and Mitophagy via an AMPK/OPA1 Signaling Pathway
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Melatonin suppresses markers of inflammation and oxidative damage in a human daytime endotoxemia model
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Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction
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Melatonin Protects against Lung Fibrosis by Regulating the Hippo/YAP Pathway
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Melatonin protects against COPD by attenuating apoptosis and endoplasmic reticulum stress via upregulating SIRT1 expression in rats
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Variations in melatonin levels in preterm and term human breast milk during the first month after delivery
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Melatonin ameliorates calcium homeostasis in myocardial and ischemia–reperfusion injury in chronically hypoxic rats
Yeung, H. M., Hung, M., & Fung, M. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00601.x · Cited by 58 · see citing works
Evidence supporting the use of melatonin in short gestation infants
Jan, J. E., Wasdell, M. B., Fréeman, R. D., & BAX, M. C. O. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00398.x · Cited by 58 · see citing works
Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction
Liu, Y., Li, L., Guo, S., Zhao, X., Liu, Y., Liang, C., Tu, S., Wang, D., Li, L., Dong, J., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.07.007 · Cited by 57 · see citing works
Melatonin receptor agonist protects against acute lung injury induced by ventilator through up-regulation of IL-10 production
Wu, G.-C., Peng, C., Liao, W.-I., Pao, H., Huang, K., & Chu, S.-J. (2020) · Respiratory Research · doi:10.1186/s12931-020-1325-2 · Cited by 56 · see citing works
Fetal/placental regulation of maternal melatonin in rats
Tamura, H., Takayama, H., Nakamura, Y., Reiter, R. J., & Sugino, N. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00537.x · Cited by 55 · see citing works
Melatonin enhances antioxidant molecules in the placenta, reduces secretion of soluble fms-like tyrosine kinase 1 (sFLT) from primary trophoblast but does not rescue endothelial dysfunction: An evaluation of its potential to treat preeclampsia
Hannan, N. J., Binder, N. K., Beard, S., Nguyen, T. V., Kaitu’u‐Lino, T. J., & Tong, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0187082 · Cited by 54 · see citing works
The reduction in circulating levels of melatonin may be associated with the development of preeclampsia
Zeng, K., Gao, Y., Wan, J., Tong, M., Lee, A. C.-L., Zhao, M., & Chen, Q. (2016) · Journal of Human Hypertension · doi:10.1038/jhh.2016.37 · Cited by 53 · see citing works
Administration of melatonin for prevention of preterm birth and fetal brain injury associated with premature birth in a mouse model
Lee, J. Y., Song, H., Oyunbileg, D., Park, M., Shin, N. E., McLane, M. W., Lei, J., Hwang, J. Y., & Burd, I. D. (2019) · American Journal of Reproductive Immunology · doi:10.1111/aji.13151 · Cited by 52 · see citing works
Relation of Nocturnal Melatonin Levels to C-Reactive Protein Concentration in Patients With ST-Segment Elevation Myocardial Infarction
Domínguez‐Rodríguez, A., García‐González, M. J., Abreu-González, P., Ferrer, J., & Kaski, J. C. (2005) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.07.120 · Cited by 51 · see citing works
Melatonin Attenuates Pulmonary Hypertension in Chronically Hypoxic Rats
Hung, M., Yeung, H. M., Lau, C., Poon, A. M. S., Tipoe, G. L., & Fung, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061125 · Cited by 49 · see citing works
Antenatal melatonin modulates an enhanced antioxidant/pro-oxidant ratio in pulmonary hypertensive newborn sheep
González‐Candia, A., Veliz, M., Carrasco‐Pozo, C., Castillo, R. L., Cárdenas, C., Ebensperger, G., Reyes, R. V., Llanos, A. J., & Herrera, E. A. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101128 · Cited by 49 · see citing works
Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol
Hobson, S. R., Lim, R., Gardiner, E. E., Alers, N. O., & Wallace, E. M. (2013) · BMJ Open · doi:10.1136/bmjopen-2013-003788 · Cited by 48 · see citing works
Melatonin regulates the calcium‐buffering proteins, parvalbumin and hippocalcin, in ischemic brain injury
Koh, P. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2012.01005.x · Cited by 48 · see citing works
Circadian influences on myocardial infarction
Virag, J. A. I., & Lust, R. M. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00422 · Cited by 46 · see citing works
The effects of melatonin supplementation on inflammatory markers among patients with metabolic syndrome or related disorders: a systematic review and meta-analysis of randomized controlled trials
Akbari, M., Ostadmohammadi, V., Tabrizi, R., Lankarani, K. B., Heydari, S. T., Amirani, E., Reiter, R. J., & Asemi, Z. (2018) · Inflammopharmacology · doi:10.1007/s10787-018-0508-7 · Cited by 46 · see citing works
Antioxidative Efficacy of a Pistacia Lentiscus Supplement and Its Effect on the Plasma Amino Acid Profile in Inflammatory Bowel Disease: A Randomised, Double-Blind, Placebo-Controlled Trial
Papada, E., Forbes, A., Amerikanou, C., Torović, L. D., Kalogeropoulos, N., Tzavara, C. K., Triantafillidis, J. K., & Kaliora, A. C. (2018) · Nutrients · doi:10.3390/nu10111779 · Cited by 46 · see citing works
Melatonin attenuates doxorubicin‐induced cardiotoxicity through preservation of YAP expression
Li, H., Wang, C., Sun, P., Liu, D., Du, G., & Tian, J. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15057 · Cited by 45 · see citing works
The effect of myocardial infarction on the synthesis, concentration and receptor expression of endogenous melatonin
Sallinen, P., Mänttäri, S. K., Leskinen, H. K., Ilves, M., Vakkuri, O., Ruskoaho, H. J., & Saarela, S. Y. O. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00413.x · Cited by 44 · see citing works
Glucose: A vital toxin and potential utility of melatonin in protecting against the diabetic state
Korkmaz, A., Ma, S., Topal, T., Rosales‐Corral, S., Tan, D., & Reiter, R. J. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.10.013 · Cited by 42 · see citing works
Anti‐inflammatory effects of melatonin in a rat model of caerulein‐induced acute pancreatitis
Carrasco, C., Marchena, A. M., Holguín‐Arévalo, M. S., Martín‐Partido, G., Rodríguez, A. B., Paredes, S. D., & Pariente, J. A. (2013) · Cell Biochemistry and Function · doi:10.1002/cbf.2942 · Cited by 41 · see citing works
Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide
Dayoub, J. C., Ortiz, F., López, L. C., Venegas, C., del Pino-Zumaquero, A., Roda, O., Sánchez‐Montesinos, I., Acuña-Castroviejo, D., & Escames, G. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00892.x · Cited by 40 · see citing works
Piromelatine, a novel melatonin receptor agonist, stabilizes metabolic profiles and ameliorates insulin resistance in chronic sleep restricted rats
She, M., Hu, X., Su, Z., Zhang, C., Yang, S., Ding, L., Laudon, M., & Yin, W. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.01.037 · Cited by 39 · see citing works
Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin
Rezzani, R., Favero, G., Stacchiotti, A., & Rodella, L. F. (2012) · Life Sciences · doi:10.1016/j.lfs.2012.11.011 · Cited by 39 · see citing works
The Effect of Preoperative Melatonin on Nuclear Erythroid 2-Related Factor 2 Activation in Patients Undergoing Coronary Artery Bypass Grafting Surgery
Javanmard, S. H., Ziaei, A., Ziaei, S., Ziaei, E., & Mirmohammadsadeghi, M. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/676829 · Cited by 39 · see citing works
Plasma 8-isoPGF2α and serum melatonin levels in patients with minimal cognitive impairment and Alzheimer disease
ŞİRİN, F. B., Doğuç, D. K., Vural, H., Eren, İ., İnanlı, İ., Sütçü, R., & Delibaş, N. (2015) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.3906/sag-1406-134 · Cited by 39 · see citing works
Maternal Melatonin Therapy Attenuates Methyl-Donor Diet-Induced Programmed Hypertension in Male Adult Rat Offspring
Tain, Y., Chan, J. Y. H., Lee, C., & Hsu, C. (2018) · Nutrients · doi:10.3390/nu10101407 · Cited by 39 · see citing works
Identification of Mel1a melatonin receptors in the human embryonic kidney cell line HEK293: evidence of G protein‐coupled melatonin receptors which do not mediate the inhibition of stimulated cyclic AMP levels
Conway, S., Drew, J. E., Canning, S. J., Barrett, P., Jockers, R., Strosberg, A. D., Lemaître, B. J., Delagrange, P., & Morgan, P. J. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00315-3 · Cited by 37 · see citing works
Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study
Kaur, S., Teoh, A. N., Shukri, N. H. M., Shafie, S. R., Bustami, N. A., Takahashi, M., Lim, P. J., & Shibata, S. (2020) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-020-2797-2 · Cited by 37 · see citing works
Roles of melatonin and its receptors in cardiac ischemia–reperfusion injury
Singhanat, K., Apaijai, N., Chattipakorn, S. C., & Chattipakorn, N. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2905-x · Cited by 36 · see citing works
Alzheimer’s disease: roles for mitochondrial damage, the hydroxyl radical, and cerebrospinal fluid deficiency of melatonin
MAURIZI, C. P. (2001) · Medical Hypotheses · doi:10.1054/mehy.2001.1324 · Cited by 35 · see citing works
Melatonin is associated with reverse remodeling after cardiac resynchronization therapy in patients with heart failure and ventricular dyssynchrony
Domínguez‐Rodríguez, A., Abreu-González, P., Piccolo, R., Galasso, G., & Reiter, R. J. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.07.056 · Cited by 35 · see citing works
A nested case–control study of the association between melatonin secretion and incident myocardial infarction
McMullan, C. J., Rimm, E. B., Schernhammer, E. S., & Forman, J. P. (2016) · Heart · doi:10.1136/heartjnl-2016-310098 · Cited by 35 · see citing works
Long-term administration of melatonin attenuates neuroinflammation in the aged mouse brain
Permpoonputtana, K., Tangweerasing, P., Mukda, S., Boontem, P., Nopparat, C., & Govitrapong, P. (2018) · EXCLI journal · doi:10.17179/excli2017-654 · Cited by 35 · see citing works
Plasma levels of melatonin in dilated cardiomyopathy
Misaka, T., Yoshihisa, A., Yokokawa, T., Sato, T., Oikawa, M., Kobayashi, A., Yamaki, T., Sugimoto, K., Kunii, H., Nakazato, K., et al. (2019) · Journal of Pineal Research · doi:10.1111/jpi.12564 · Cited by 34 · see citing works
Role of melatonin as an SIRT1 enhancer in chronic obstructive pulmonary disease induced by cigarette smoke
Shin, N., Ko, J., Kim, J., Park, G., Kim, S., Kim, M., Kim, J., & Shin, I. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14816 · Cited by 34 · see citing works
Aanat Knockdown and Melatonin Supplementation in Embryo Development: Involvement of Mitochondrial Function and DNA Methylation
Yang, M., Tao, J., Wu, H., Guan, S., Liu, L., Zhang, L., Deng, S., He, C., Ji, P., Liu, J., et al. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7555 · Cited by 33 · see citing works
Ramelteon attenuates age‐associated hypertension and weight gain in spontaneously hypertensive rats
Oxenkrug, G. F., & D, P. S. M. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05355.x · Cited by 32 · see citing works
Melatonin in Cardiac Ischemia/Reperfusion-Induced Mitochondrial Adaptive Changes
Giacomo, C., & Marchi, A. (2007) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/187152907781745297 · Cited by 32 · see citing works
Relationship between melatonin secretion and nighttime blood pressure in elderly individuals with and without antihypertensive treatment: a cross-sectional study of the HEIJO-KYO cohort
Obayashi, K., Saeki, K., Tone, N., & Kurumatani, N. (2014) · Hypertension Research · doi:10.1038/hr.2014.99 · Cited by 31 · see citing works
Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole – a melatonin membrane receptors inhibitor
Drobnik, J., Owczarek, K., Piera, L., Tosik, D., Olczak, S., Ciosek, J., & Hrabec, E. (2013) · Pharmacological Reports · doi:10.1016/s1734-1140(13)71041-7 · Cited by 31 · see citing works
Effects of intracoronary melatonin on ischemia–reperfusion injury in ST-elevation myocardial infarction
Ekeloef, S., Halladin, N., Jensen, S. E., Zaremba, T., Aarøe, J., Kjærgaard, B., Simonsen, C. W., Rosenberg, J., & Gögenür, I. (2014) · Heart and Vessels · doi:10.1007/s00380-014-0589-1 · Cited by 31 · see citing works
Elevated serum melatonin levels during human late pregnancy and labour
WIERRANI, W. G. F. (1997) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443619750112411 · Cited by 30 · see citing works
Protective actions of melatonin and growth hormone on the aged cardiovascular system
Paredes, S. D., Forman, K., Garcı́a, C., Vara, E., Escames, G., & Tresguerres, J. A. F. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0016 · Cited by 30 · see citing works
Effect of oral melatonin on the procoagulant response to acute psychosocial stress in healthy men: a randomized placebo‐controlled study
Wirtz, P. H., Bärtschi, C., Spillmann, M., Ehlert, U., & von Känel, R. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00535.x · Cited by 29 · see citing works

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2 of the 223 references couldn’t be matched to a known paper.

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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Signaling pathways and targeted therapy for myocardial infarction
Zhang, Q., Wang, L., Wang, S., Cheng, H., Xu, L., Pei, G., Wang, Y., Fu, C., Jiang, Y., He, C., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00925-z · Cited by 855 · see citing works
Polystyrene nanoplastic exposure induces excessive mitophagy by activating AMPK/ULK1 pathway in differentiated SH-SY5Y cells and dopaminergic neurons in vivo
Huang, Y., Liang, B., Li, Z., Zhong, Y., Wang, B., Zhang, B., Du, J., Ye, R., Xian, H., Min, W., et al. (2023) · Particle and Fibre Toxicology · doi:10.1186/s12989-023-00556-4 · Cited by 199 · see citing works
Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
“Melatonin is derived from serotonin using 5-hydroxytryptophan (5-HTP) and tryptophan [32,55].”
BackgroundMethodInfluential
Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression
Beltrán-García, J., Osca-Verdegal, R., Pallardó, F. V., Ferreres, J., Rodríguez, M. D. P., Mulet, S., Sanchis‐Gomar, F., Carbonell, N., & García‐Giménez, J. L. (2020) · Antioxidants · doi:10.3390/antiox9100936 · Cited by 161 · see citing works
Immunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 157 · see citing works
Melatonin attenuates LPS-induced pyroptosis in acute lung injury by inhibiting NLRP3-GSDMD pathway via activating Nrf2/HO-1 signaling axis
Kang, J., Xu, M., Sun, Y., Ding, Z., Wei, Y., Zhang, D.-W., Wang, Y., Shen, J., Wu, H., & Fei, G. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108782 · Cited by 133 · see citing works
Melatonin: the placental antioxidant and anti-inflammatory
Joseph, T. T., Schuch, V., Hossack, D. J., Chakraborty, R., & Johnson, E. L. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1339304 · Cited by 112 · see citing works
New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy
Victor, S., Rocha‐Ferreira, E., Rahim, A. A., Hagberg, H., & Edwards, A. D. (2021) · European Journal of Pediatrics · doi:10.1007/s00431-021-04320-8 · Cited by 101 · see citing works
Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action
Muñoz-Jurado, A., Escribano, B. M., Caballero‐Villarraso, J., Galván, A., Agüera, E., Santamarı́a, A., & Túnez, I. (2022) · Inflammopharmacology · doi:10.1007/s10787-022-01011-0 · Cited by 97 · see citing works
Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy
Ranjan, A. K., & Gulati, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206653 · Cited by 111 · see citing works
Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment
Hou, R., Lu, T., Gao, W., Shen, J., Yu, Z., Li, D., Zhang, R., Zheng, Y., & Cai, X. (2022) · ACS Nano · doi:10.1021/acsnano.2c02832 · Cited by 85 · see citing works
A rapid review of the pathoetiology, presentation, and management of delirium in adults with COVID-19
Hawkins, M., Sockalingam, S., Bonato, S., Rajaratnam, T., Ravindran, M., Gosse, P. J., & Sheehan, K. (2020) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2020.110350 · Cited by 79 · see citing works
Melatonin as the Cornerstone of Neuroimmunoendocrinology
Kvetnoy, I. M., Иванов, Д. О., Mironova, E. S., Evsyukova, I. I., Nasyrov, R. A., Kvetnaia, T. V., & Polyakova, V. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031835 · Cited by 78 · see citing works
A Systematic Review on Advances in Management of Oxidative Stress-Associated Cardiovascular Diseases
Jin, S., & Kang, P. M. (2024) · Antioxidants · doi:10.3390/antiox13080923 · Cited by 81 · see citing works
Protective actions of nuclear factor erythroid 2-related factor 2 (NRF2) and downstream pathways against environmental stressors
Jiménez, M. T. B., Frenis, K., Hahad, O., Steven, S., Cohen, G., Cuadrado, A., Münzel, T. F., & Daiber, A. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.05.016 · Cited by 74 · see citing works
Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging
Mladenov, M. I., Lubomirov, L. T., Grisk, O., Avtanski, D. B., Mitrokhin, V. M., Sazdova, I., Keremidarska‐Markova, M., Danailova, Y., Nikolaev, G., Konakchieva, R., et al. (2023) · Antioxidants · doi:10.3390/antiox12051126 · Cited by 74 · see citing works
COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception—A Systematic Review
Wijeratne, T., Crewther, S. G., Sales, C., & Karimi, L. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.607221 · Cited by 75 · see citing works
Engineered Extracellular Vesicles Modified by Angiopep-2 Peptide Promote Targeted Repair of Spinal Cord Injury and Brain Inflammation
Kong, G., Liu, J., Wang, J., Yu, X., Li, C., Deng, M., Liu, M., Wang, S., Tang, C., Xiong, W., et al. (2025) · ACS Nano · doi:10.1021/acsnano.4c14675 · Cited by 72 · see citing works
Melatonin prevents conjugative transfer of plasmid-mediated antibiotic resistance genes by disrupting proton motive force
Jia, Y., Yang, B., Shi, J., Fang, D., Wang, Z., & Liu, Y. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105978 · Cited by 70 · see citing works
Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights
He, F., Wu, X., Zhang, Q., Li, Y., Ye, Y., Li, P., Chen, S., Peng, Y., Hardeland, R., & Xia, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.683879 · Cited by 65 · see citing works
Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye
Wang, B., Zuo, X., Peng, L., Wang, X., Zeng, H., Zhong, J., Li, S., Xiao, Y., Wang, L., Ouyang, H. W., et al. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108491 · Cited by 60 · see citing works
Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions
Ieșanu, M. I., Zahiu, C. D. M., Dogaru, I.-A., Chiţimuș, D. M., Pîrcălăbioru, G. G., Voiculescu, S. E., Isac, S., Galoş, F., Pavel, B., O’Mahony, S. M., et al. (2022) · Antioxidants · doi:10.3390/antiox11112244 · Cited by 60 · see citing works
Self-citation
Certain Fermented Foods and Their Possible Health Effects with a Focus on Bioactive Compounds and Microorganisms
Deveci, G., Çelik, E., Ağagündüz, D., Bartkienė, E., Rocha, J. M., & Özoğul, F. (2023) · Fermentation · doi:10.3390/fermentation9110923 · Cited by 52 · see citing works
Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement
Kamfar, W. W., Khraiwesh, H. M., Ibrahim, M. O., Qadhi, A., Azhar, W. F., Ghafouri, K. J., Alhussain, M. H., Aldairi, A. F., AlShahrani, A. M., Alghannam, A. F., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e24266 · Cited by 56 · see citing works
A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy
Korf, J. M., McCullough, L. D., & Caretti, V. (2023) · Translational Pediatrics · doi:10.21037/tp-23-253 · Cited by 45 · see citing works
Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds
Hardeland, R. (2021) · Molecules · doi:10.3390/molecules26134105 · Cited by 45 · see citing works
Melatonin for the Early Treatment of COVID-19: A Narrative Review of Current Evidence and Possible Efficacy
Cross, K. M., Landis, D. M., Sehgal, L., & Payne, J. D. (2021) · Endocrine Practice · doi:10.1016/j.eprac.2021.06.001 · Cited by 41 · see citing works
BPS‐induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT‐1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT‐4 expressions in adult golden hamster
Pal, S., Sahu, A., Verma, R., & Haldar, C. (2023) · Journal of Pineal Research · doi:10.1111/jpi.12869 · Cited by 43 · see citing works
Advances in the modulation of ROS and transdermal administration for anti-psoriatic nanotherapies
Xu, J., Chen, H., Qian, H., Wang, F., & Xu, Y. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01651-y · Cited by 40 · see citing works
Exosomes and Melatonin: Where Their Destinies Intersect
Novais, A. A., Chuffa, L. G. D. A., Zuccari, D. A. P. D. C., & Reiter, R. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.692022 · Cited by 38 · see citing works
Melatonin exerts a protective effect in ameliorating nephrolithiasis via targeting AMPK/PINK1-Parkin mediated mitophagy and inhibiting ferroptosis in vivo and in vitro
Zhou, J., Meng, L., He, Z., Song, Q., Liu, J., Su, X., Wang, C., Hu, K., Dong, C., Liao, W., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110801 · Cited by 36 · see citing works
Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice
Khafaji, A. W. M., Al-Zubaidy, A. A., Farhood, I. G., & Salman, H. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03017-7 · Cited by 36 · see citing works
Melatonin inhibits proliferation and viability and promotes apoptosis in colorectal cancer cells via upregulation of the microRNA-34a/449a cluster
Ji, G., Zhou, W., Li, X., Du, J., Li, X., & Hao, H. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.11826 · Cited by 36 · see citing works
Oxidative Imbalance in Endometriosis-Related Infertility—The Therapeutic Role of Antioxidants
Dymanowska-Dyjak, I., Frankowska, K., Abramiuk, M., & Polak, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126298 · Cited by 34 · see citing works
Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress
Elkamhawy, A., Woo, J., Gouda, N. A., Kim, J., Nada, H., Roh, E. J., Park, K. D., Cho, J., & Lee, K. (2021) · Antioxidants · doi:10.3390/antiox10101604 · Cited by 34 · see citing works
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Authors: Chitimus, D. M., Popescu, M. R., Voiculescu, S. E., Panaitescu, A. M., Pavel, B., Zagrean, L., & Zagrean, A.-M.
Affiliations: Division of Physiology and Neuroscience, Department of Functional Sciences, “Carol Davila” University of Medicine and Pharmacy, 010164 Bucharest, Romania
Carol Davila University of Medicine and Pharmacy (RO)
ORCID: Popescu, Mihaela Roxana
Voiculescu, Suzana Elena
Panaitescu, Anca Maria
Pavel, Bogdan
Zagrean, Ana-Maria
Venue: Biomolecules
Publisher: MDPI AG
Published: 2020-08-20
Volume: 10
Issue: 9
Pages: 1211
ISSN: 2218-273X (ISSN-L)
DOI: 10.3390/biom10091211
PMC: PMC7563541
OpenAlex: W3058036789
Semantic Scholar: 262cbe3526edc06c7fcb8c018bdcb2a802d687a3
Cited by: 354
References: 223
Citations by year: 2026: 52 · 2025: 85 · 2024: 70 · 2023: 65 · 2022: 53 · 2021: 26 · 2020: 2 · 2013: 1
FWCI: 4.97
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Biomolecules (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords: melatonin, antioxidant activity, anti-inflammatory activity, oxidative stress, inflammation, allostasis, pregnancy, offspring survival, hypertension, myocardial ischemia-reperfusion injury, cardiovascular disease, metabolic syndrome, neurodegenerative diseases, COVID-19 treatment, melatonin supplementation
MeSH terms: COVID-19, Adjuvants, Pharmaceutic, Animals, Anti-Inflammatory Agents, Antioxidants, Homeostasis, Humans, Melatonin, Pneumonia, Viral, Coronavirus Infections, Pandemics

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Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease

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