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Nutrients Sep 2021Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this... (Review)
Review
Sleep is an essential component of overall human health but is so tightly regulated that when disrupted can cause or worsen certain ailments. An important part of this process is the presence of the well-known hormone, melatonin. This compound assists in the governing of sleep and circadian rhythms. Previous studies have postulated that dysregulation of melatonin rhythms is the driving force behind sleep and circadian disorders. A computer-aided search spanning the years of 2015-2020 using the search terms melatonin, circadian rhythm, disorder yielded 52 full text articles that were analyzed. We explored the mechanisms behind melatonin dysregulation and how it affects various disorders. Additionally, we examined associated therapeutic treatments including bright light therapy (BLT) and exogenous forms of melatonin. We found that over the past 5 years, melatonin has not been widely investigated in clinical studies thus there remains large gaps in its potential utilization as a therapy.
Topics: Animals; Biosynthetic Pathways; Circadian Rhythm; Humans; Light; Melatonin; Transcription, Genetic
PubMed: 34684482
DOI: 10.3390/nu13103480 -
Neuro-Chirurgie 2015Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is... (Review)
Review
Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal light/dark conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas under field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlations between clinical observations and melatonin secretion, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions depend also on the melatonin signal, for instance immune, antioxidant defences, haemostasis and glucose regulation. The difference between physiological and pharmacological effects of melatonin is not always clear but is based upon consideration of dose and not of duration of the hormone message. It is admitted that a "physiological" dose provides plasma melatonin levels in the same order of magnitude as a nocturnal peak. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where melatonin secretion can be disturbed. The resulting alteration could increase the predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder. Since melatonin receptors display a very wide distribution in the body, putative therapeutic indications of this compound are multiple. Great advances in this field could be achieved by developing multicentre trials in a large series of patients, in order to establish efficacy of melatonin and absence of long-term toxicity.
Topics: Animals; Brain; Circadian Rhythm; Humans; Light; Melatonin; Seasons; Sleep
PubMed: 25908646
DOI: 10.1016/j.neuchi.2015.03.002 -
Physiology (Bethesda, Md.) Sep 2014Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm... (Review)
Review
Melatonin is a small, highly conserved indole with numerous receptor-mediated and receptor-independent actions. Receptor-dependent functions include circadian rhythm regulation, sleep, and cancer inhibition. The receptor-independent actions relate to melatonin's ability to function in the detoxification of free radicals, thereby protecting critical molecules from the destructive effects of oxidative stress under conditions of ischemia/reperfusion injury (stroke, heart attack), ionizing radiation, and drug toxicity, among others. Melatonin has numerous applications in physiology and medicine.
Topics: Animals; Circadian Rhythm; Free Radicals; Humans; Melatonin; Oxidative Stress; Signal Transduction; Treatment Outcome
PubMed: 25180262
DOI: 10.1152/physiol.00011.2014 -
Molecular and Cellular Biochemistry Dec 2019Melatonin (N-acetyl-5-methoxy-tryptamine), which is generally considered as pleiotropic and multitasking molecule, secretes from pineal gland at night under normal light... (Review)
Review
Melatonin (N-acetyl-5-methoxy-tryptamine), which is generally considered as pleiotropic and multitasking molecule, secretes from pineal gland at night under normal light or dark conditions. Apart from circadian regulations, Melatonin also has antioxidant, anti-ageing, immunomodulation and anticancer properties. From the epidemiological research, it was postulated that Melatonin has significant apoptotic, angiogenic, oncostatic and anti-proliferative effects on various oncological cells. In this review, the underlying anticancer mechanisms of Melatonin such as stimulation of apoptosis, Melatonin receptors (MT1 and MT2) stimulation, paro-survival signal regulation, the hindering of angiogenesis, epigenetic alteration and metastasis have been discussed with recent findings. The Melatonin utilization as an adjuvant with chemotherapeutic drugs for the reinforcement of therapeutic effects was also discussed. This review precisely emphasizes the anticancer effect of Melatonin on various cancer cells. This review exemplifies the epidemiology and anticancer efficiency of Melatonin with prior attention to the mechanisms of actions.
Topics: Animals; Antineoplastic Agents; Antioxidants; Clinical Trials as Topic; Humans; Melatonin
PubMed: 31451998
DOI: 10.1007/s11010-019-03617-5 -
Ageing Research Reviews Jun 2022Osteoarthritis (OA), characterized by cartilage erosion, synovium inflammation, and subchondral bone remodeling, is a common joint degenerative disease worldwide. OA... (Review)
Review
Osteoarthritis (OA), characterized by cartilage erosion, synovium inflammation, and subchondral bone remodeling, is a common joint degenerative disease worldwide. OA pathogenesis is regulated by multiple predisposing factors, including imbalanced matrix metabolism, aberrant inflammatory response, and excessive oxidative stress. Moreover, melatonin has been implicated in development of several degenerative disorders owing to its potent biological functions. With regards to OA, melatonin reportedly promotes synthesis of cartilage matrix, inhibition of chondrocyte apoptosis, attenuation of inflammatory response, and suppression of matrix degradation by regulating the TGF-β, MAPK, or NF-κB signaling pathways. Notably, melatonin has been associated with amelioration of oxidative damage by restoring the OA-impaired intracellular antioxidant defense system in articular cartilage. Findings from preliminary application of melatonin or melatonin-loaded biomaterials in animal models have affirmed its potential anti-arthritic effects. Herein, we summarize the anti-arthritic effects of melatonin on OA cartilage and demonstrate that melatonin has potential therapeutic efficacy in treating OA.
Topics: Animals; Apoptosis; Cartilage, Articular; Chondrocytes; Humans; Melatonin; Osteoarthritis
PubMed: 35483626
DOI: 10.1016/j.arr.2022.101635 -
Journal of Pineal Research Oct 2016Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct... (Review)
Review
Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.
Topics: Animals; Antioxidants; Apoptosis; Humans; Melatonin; Myocardial Reperfusion Injury; Oxidative Stress; Stroke
PubMed: 27500468
DOI: 10.1111/jpi.12360 -
Biomolecules Aug 2020There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis,... (Review)
Review
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.
Topics: Adjuvants, Pharmaceutic; Animals; Anti-Inflammatory Agents; Antioxidants; COVID-19; Coronavirus Infections; Homeostasis; Humans; Melatonin; Pandemics; Pneumonia, Viral
PubMed: 32825327
DOI: 10.3390/biom10091211 -
Annals of Botany Feb 2018Plant melatonin appears to be a multi-regulatory molecule, similar to those observed in animals, with many specific functions in plant physiology. In recent years, the... (Review)
Review
BACKGROUND
Plant melatonin appears to be a multi-regulatory molecule, similar to those observed in animals, with many specific functions in plant physiology. In recent years, the number of studies on melatonin in plants has increased significantly. One of the most studied actions of melatonin in plants is its effect on biotic and abiotic stress, such as that produced by drought, extreme temperatures, salinity, chemical pollution and UV radiation, among others.
SCOPE
This review looks at studies in which some aspects of the relationship between melatonin and the plant hormones auxin, cytokinin, gibberellins, abscisic acid, ethylene, jasmonic acid and salicylic acid are presented. The effects that some melatonin treatments have on endogenous plant hormone levels, their related genes (biosynthesis, catabolism, receptors and transcription factors) and the physiological actions induced by melatonin, mainly in stress conditions, are discussed.
CONCLUSIONS
Melatonin is an important modulator of gene expression related to plant hormones, e.g. in auxin carrier proteins, as well as in metabolism of indole-3-acetic acid (IAA), gibberellins, cytokinins, abscisic acid and ethylene. Most of the studies performed have dealt with the auxin-like activity of melatonin which, in a similar way to IAA, is able to induce growth in shoots and roots and stimulate root generation, giving rise to new lateral and adventitious roots. Melatonin is also able to delay senescence, protecting photosynthetic systems and related sub-cellular structures and processes. Also, its role in fruit ripening and post-harvest processes as a gene regulator of ethylene-related factors is relevant. Another decisive aspect is its role in the pathogen-plant interaction. Melatonin appears to act as a key molecule in the plant immune response, together with other well-known molecules such as nitric oxide and hormones, such as jasmonic acid and salicylic acid. In this sense, the discovery of elevated levels of melatonin in endophytic organisms associated with plants has thrown light on a possible novel form of communication between beneficial endophytes and host plants via melatonin.
Topics: Melatonin; Plant Growth Regulators; Plant Physiological Phenomena; Plants
PubMed: 29069281
DOI: 10.1093/aob/mcx114 -
Frontiers in Endocrinology 2020For more than a half century the hormone melatonin has been associated with vertebrate reproduction, particularly in the context of seasonal breeding. This association... (Review)
Review
For more than a half century the hormone melatonin has been associated with vertebrate reproduction, particularly in the context of seasonal breeding. This association is due in large measure to the fact that melatonin secretion from the pineal gland into the peripheral circulation is a nocturnal event whose duration is reflective of night length, which of course becomes progressively longer during winter months and correspondingly shorter during the summer months. The nocturnal plasma melatonin signal is conserved in essentially all vertebrates and is accessed not just for reproductive rhythms, but for seasonal cycles of metabolic activities, immune functions, and behavioral expression. A vast literature on melatonin and vertebrate biology has accrued over the past 60 years since melatonin's discovery, including the broad topic of animal reproduction, which is far beyond the scope of this human-focused review. Although modern humans in the industrialized world appear in general to have little remaining reproductive seasonality, the relationships between melatonin and human reproduction continue to attract widespread scientific attention. The purpose of this chapter is to draw attention to some newer developments in the field, especially those with relevance to human fertility and reproductive medicine. As the vast majority of studies have focused on the female reproductive system, a discussion of the potential impact of melatonin on human male fertility will be left for others.
Topics: Animals; Circadian Rhythm; Female; Genitalia, Female; Humans; Melatonin; Reproduction
PubMed: 32210911
DOI: 10.3389/fendo.2020.00085 -
International Journal of Molecular... Dec 2022Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of... (Review)
Review
Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin's benefit in anxiety may reside in its sympatholytic action, interaction with the renin-angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
Topics: Animals; Melatonin; Anti-Anxiety Agents; Antioxidants; Free Radicals; Anxiety
PubMed: 36555831
DOI: 10.3390/ijms232416187