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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 -
Biomolecules Jun 2023Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from... (Review)
Review
Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been administered to patients, including the elderly and children, in clinical trials. In this review, we critically review the corresponding literature, including the hypotheses that melatonin acts as a scavenger molecule, in particular in mitochondria, by trying not only to contextualize these interests but also by attempting to separate the wheat from the chaff (or the wishful thinking from the facts). We conclude that most claims remain hypotheses and that the experimental evidence used to promote them is limited and sometimes flawed. Our review will hopefully encourage clinical researchers to reflect on what melatonin can and cannot do and help move the field forward on a solid basis.
Topics: Animals; Melatonin; Mitochondria
PubMed: 37371523
DOI: 10.3390/biom13060943 -
JAMA Apr 2023
Topics: Cannabidiol; Cannabis; Melatonin; Administration, Oral; United States; Dosage Forms
PubMed: 37097362
DOI: 10.1001/jama.2023.2296 -
Molecules (Basel, Switzerland) Oct 2015Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in... (Review)
Review
Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin's synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.
Topics: Animals; Antioxidants; Biosynthetic Pathways; Humans; Melatonin; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species
PubMed: 26501252
DOI: 10.3390/molecules201018886 -
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 -
Microbiome Jan 2023Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can...
Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.
Topics: Animals; Mice; Sleep Deprivation; Gastrointestinal Microbiome; Melatonin; Neuroprotective Agents; Lipopolysaccharides; Toll-Like Receptor 4; Butyrates; Clostridiales; Cognitive Dysfunction
PubMed: 36721179
DOI: 10.1186/s40168-022-01452-3 -
Molecules (Basel, Switzerland) Jan 2018The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective... (Review)
Review
The pineal gland is a unique organ that synthesizes melatonin as the signaling molecule of natural photoperiodic environment and as a potent neuronal protective antioxidant. An intact and functional pineal gland is necessary for preserving optimal human health. Unfortunately, this gland has the highest calcification rate among all organs and tissues of the human body. Pineal calcification jeopardizes melatonin's synthetic capacity and is associated with a variety of neuronal diseases. In the current review, we summarized the potential mechanisms of how this process may occur under pathological conditions or during aging. We hypothesized that pineal calcification is an active process and resembles in some respects of bone formation. The mesenchymal stem cells and melatonin participate in this process. Finally, we suggest that preservation of pineal health can be achieved by retarding its premature calcification or even rejuvenating the calcified gland.
Topics: Aging; Animals; Calcinosis; Humans; Melatonin; Pineal Gland; Rejuvenation
PubMed: 29385085
DOI: 10.3390/molecules23020301 -
Current Neuropharmacology 2023The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this... (Review)
Review
The use of exogenous melatonin (exo-MEL) as a sleep-promoting drug has been under extensive debate due to the lack of consistency of its described effects. In this study, we conduct a systematic and comprehensive review of the literature on the chronobiotic, sleep-inducing, and overall sleep-promoting properties of exo-MEL. To this aim, we first describe the possible pharmacological mechanisms involved in the sleep-promoting properties and then report the corresponding effects of exo-MEL administration on clinical outcomes in: a) healthy subjects, b) circadian rhythm sleep disorders, c) primary insomnia. Timing of administration and doses of exo-MEL received particular attention in this work. The exo-MEL pharmacological effects are hereby interpreted in view of changes in the physiological properties and rhythmicity of endogenous melatonin. Finally, we discuss some translational implications for the personalized use of exo-MEL in the clinical practice.
Topics: Humans; Melatonin; Circadian Rhythm; Sleep
PubMed: 35176989
DOI: 10.2174/1570159X20666220217152617 -
Archives of Endocrinology and Metabolism Aug 2018Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal... (Review)
Review
Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.
Topics: Circadian Rhythm; Humans; Melatonin; Sleep Wake Disorders
PubMed: 30304113
DOI: 10.20945/2359-3997000000066 -
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