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British Journal of Pharmacology Aug 2018This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this...
This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.
Topics: Animals; Circadian Rhythm; Humans; Melatonin; Mental Disorders; Neoplasms; Nervous System Diseases; Pineal Gland; Receptors, Melatonin; Sleep
PubMed: 30917240
DOI: 10.1111/bph.14371 -
American Journal of Alzheimer's Disease... Mar 2015The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the... (Review)
Review
The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the elderly patients from randomized controlled trials (RCTs). A systematic search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane Library was conducted. This search yielded a total of 2 RCTs for melatonin. One study compared melatonin to midazolam, clonidine, and control groups for the prevention and management of delirium in individuals who were pre- and posthip post-hip arthroplasty. The other study compared melatonin to placebo for the prevention of delirium in older adults admitted to an inpatient internal medicine service. Data from these 2 studies indicate that melatonin may have some benefit in the prevention and management of delirium in older adults. However, there is no evidence that melatonin reduces the severity of delirium or has any effect on behaviors or functions in these individuals. Melatonin was well tolerated in these 2 studies. The search for a melatonin agonist for delirium in the elderly patients yielded 1 study of ramelteon. In this study, ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo. Ramelteon was well tolerated in this study.
Topics: Aged; Delirium; Humans; Indenes; Melatonin; Randomized Controlled Trials as Topic
PubMed: 24946785
DOI: 10.1177/1533317514539379 -
Cellular and Molecular Life Sciences :... Nov 2017Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine,... (Review)
Review
Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin's protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.
Topics: Animals; Antioxidants; Humans; Melatonin; Mitochondria; Reperfusion Injury
PubMed: 28795196
DOI: 10.1007/s00018-017-2618-6 -
International Journal of Biological... 2023A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in...
A balance between muscle injury and regeneration is critical for sustaining muscle function during myogenesis. Melatonin is well recognized for its involvement in neuroprotective activities, immune system regulation and suppression of inflammatory responses. This study set out to provide evidence that melatonin improves muscle regeneration during skeletal muscle differentiation. We began with cloning a stable cell line expressing Pax7 knockdown C2C12 cells. We then investigated markers of muscle degradation and regeneration after treating growth medium and differentiated medium with melatonin. Bioinformatics analysis of RNA sequencing results revealed that melatonin regulates muscle differentiation and that Wnt cascades are involved in the mechanism of muscle differentiation. Screening of miRNA online databases revealed that miR-3475-3p is a specific binding site on Pax7 and acts as a negative regulator of Pax7, which is involved in melatonin-induced muscle differentiation. We then investigated the effects of melatonin treatment in the early stage of glycerol-induced skeletal muscle injury in mice. Rotarod performance, micro-computed tomography and immunohistochemistry findings showed that melatonin-induced increases in Pax7 expression rapidly rescue skeletal muscle differentiation and improve muscle fiber morphology in glycerol-induced muscle injury. Our data support the hypothesis that melatonin rapidly rescues skeletal muscle differentiation and the melatonin/Pax7 axis could therefore serve as an important therapeutic target to optimize muscle healing after injury.
Topics: Animals; Mice; Melatonin; Glycerol; X-Ray Microtomography; Myoblasts; Cell Differentiation; Muscle, Skeletal; Muscle Development; Cell Proliferation; PAX7 Transcription Factor
PubMed: 36923937
DOI: 10.7150/ijbs.79169 -
Cells Oct 2022Plant growth and development exhibit plasticity, and plants can adapt to environmental changes and stress. Various phytohormones interact synergistically or... (Review)
Review
Plant growth and development exhibit plasticity, and plants can adapt to environmental changes and stress. Various phytohormones interact synergistically or antagonistically to regulate these responses. Melatonin and indole-3-acetic acid (IAA) are widespread across plant kingdom. Melatonin, an important member of the neuroendocrine immune regulatory network, can confer autoimmunity and protect against viral invasion. Melatonin functions as a plant growth regulator and biostimulant, with an important role in enhancing plant stress tolerance. IAA has a highly complex stress response mechanism, which participates in a series of stress induced physiological changes. This article reviews studies on the signaling pathways of melatonin and IAA, focusing on specific regulatory mechanisms. We discuss how these hormones coordinate plant growth and development and stress responses. Furthermore, the interactions between melatonin and IAA and their upstream and downstream transcriptional regulation are discussed from the perspective of modulating plant development and stress adaptation. The reviewed studies suggest that, at low concentrations, melatonin promotes IAA synthesis, whereas at high levels it reduces IAA levels. Similarly to IAA, melatonin promotes plant growth and development. IAA suppresses the melatonin induced inhibition of germination. IAA signaling plays an important role in plant growth and development, whereas melatonin signaling plays an important role in stress responses.
Topics: Plant Growth Regulators; Melatonin; Indoleacetic Acids; Plant Development; Plants
PubMed: 36291118
DOI: 10.3390/cells11203250 -
Journal of Pineal Research Apr 2022The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms of action, which include the... (Review)
Review
The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms of action, which include the regulation of vertebrate pigmentation. Although first discovered through its potent skin-lightening effects in amphibians, melatonin's role in human skin and hair follicle pigmentation and its impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding of this role, we specifically examine its impact on melanogenesis, oxidative biology, mitochondrial function, melanocyte senescence, and pigmentation-related clock gene activity, with emphasis on human skin, yet without ignoring instructive pointers from nonhuman species. Given the strict dependence of melanocyte functions on the epithelial microenvironment, we underscore that melanocyte responses to melatonin are best interrogated in a physiological tissue context. Current evidence suggests that melatonin and some of its metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) and melanocyte proliferation by stimulating melatonin membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory effects of melatonin may occur via activation of Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- and cAMP-dependent signaling, and/or via melatonin-regulated changes in peripheral clock genes that regulate human melanogenesis, namely Bmal1 and Per1. Melatonin and its metabolites also accumulate in melanocytes where they exert net cyto- and senescence-protective as well as antioxidative effects by operating as free radical scavengers, stimulating the synthesis and activity of ROS scavenging enzymes and other antioxidants, promoting DNA repair, and enhancing mitochondrial function. We argue that it is clinically and biologically important to definitively clarify whether melanocyte cell culture-based observations translate into melatonin-induced pigmentary changes in a physiological tissue context, that is, in human epidermis and hair follicles ex vivo, and are confirmed by clinical trial results. After defining major open questions in this field, we close by suggesting how to begin answering them in clinically relevant, currently available preclinical in situ research models.
Topics: Hair Follicle; Humans; Melanins; Melanocytes; Melatonin; Phosphatidylinositol 3-Kinases
PubMed: 35133682
DOI: 10.1111/jpi.12790 -
Current Neuropharmacology Mar 2022Melatonin, a vital hormone synthesized by the pineal gland, has been implicated in various physiological functions and circadian rhythm regulation. Its role in the... (Review)
Review
Melatonin, a vital hormone synthesized by the pineal gland, has been implicated in various physiological functions and circadian rhythm regulation. Its role in the protection against the non-ionizing electromagnetic field (EMF), known to disrupt the body's oxidative/anti-oxidative balance, has been called into question due to inconsistent results observed across studies. This review provides the current knowledge on the interwoven relationship between melatonin, EMF, and oxidative stress. Based on synthesized evidence, we present a model that best describes the mechanisms underlying the protective effects of melatonin against RF/ELF-EMF-induced oxidative stress. It has been observed that the free radical scavenger activity of melatonin can be enabled by reducing the radical pair singlet-triplet conversion rate and the concentration of the triplet products. Moreover, this review aims to highlight the potential therapeutic benefits of melatonin against the detrimental effects of EMF, in general, and electromagnetic hypersensitivity (EHS), in particular.
Topics: Circadian Rhythm; Electromagnetic Fields; Electromagnetic Radiation; Humans; Melatonin; Oxidative Stress; Pineal Gland
PubMed: 34635042
DOI: 10.2174/1570159X19666210609163946 -
Biomolecules Mar 2023Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock.... (Review)
Review
Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin's antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.
Topics: Animals; Melatonin; Livestock; Circadian Rhythm; Antioxidants; Photoperiod
PubMed: 36979425
DOI: 10.3390/biom13030490 -
Open Heart Mar 2021A recent retrospective study has provided evidence that COVID-19 infection may be notably less common in those using supplemental melatonin. It is suggested that this...
A recent retrospective study has provided evidence that COVID-19 infection may be notably less common in those using supplemental melatonin. It is suggested that this phenomenon may reflect the fact that, via induction of silent information regulator 1 (Sirt1), melatonin can upregulate K63 polyubiquitination of the mitochondrial antiviral-signalling protein, thereby boosting virally mediated induction of type 1 interferons. Moreover, Sirt1 may enhance the antiviral efficacy of type 1 interferons by preventing hyperacetylation of high mobility group box 1 (HMGB1), enabling its retention in the nucleus, where it promotes transcription of interferon-inducible genes. This nuclear retention of HMGB1 may also be a mediator of the anti-inflammatory effect of melatonin therapy in COVID-19-complementing melatonin's suppression of nuclear factor kappa B activity and upregulation of nuclear factor erythroid 2-related factor 2. If these speculations are correct, a nutraceutical regimen including vitamin D, zinc and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and influenza.
Topics: Antioxidants; COVID-19; Humans; Melatonin; RNA Virus Infections; Risk Factors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33741691
DOI: 10.1136/openhrt-2020-001568 -
Molecules (Basel, Switzerland) Jan 2022Melatonin (MLT) is involved in many functions of the human body, mainly in sleeping-related disorders. It also has anti-oxidant potential and has been proven very... (Review)
Review
Melatonin (MLT) is involved in many functions of the human body, mainly in sleeping-related disorders. It also has anti-oxidant potential and has been proven very effective in the treatment of seasonal affective disorders (SAD), which afflict some people during short winter days. Melatonin has been implicated in a range of other conditions, including Parkinson's disease, Alzheimer's and other neurological conditions, and in certain cancers. Its poor solubility in water leads to an insufficient absorption that led scientists to investigate MLT inclusion in cyclodextrins (CDs), as inclusion of drugs in CDs is a way of increasing the solubility of many lipophilic moieties with poor water solubility. The aim of this review is to gather all the key findings on MLT/CD complexes. The literature appraisal concluded that MLT inclusion leads to a 1:1 complex with the majority of CDs and increases the solubility of the hormone. The interactions of MLT with CDs can be studied by a variety of techniques, such as NMR, FT-IR, XRD and DCS. More importantly, the in vivo experiments showed an increase in the uptake of MLT when included in a CD.
Topics: Biological Availability; Cyclodextrins; Drug Carriers; Humans; Magnetic Resonance Spectroscopy; Melatonin; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 35056757
DOI: 10.3390/molecules27020445