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International Journal of Molecular... Jan 2023As people age, their risks of developing degenerative diseases such as cancer, diabetes, Parkinson's Disease (PD), Alzheimer's Disease (AD), rheumatoid arthritis, and... (Review)
Review
As people age, their risks of developing degenerative diseases such as cancer, diabetes, Parkinson's Disease (PD), Alzheimer's Disease (AD), rheumatoid arthritis, and osteoporosis are generally increasing. Millions of people worldwide suffer from these diseases as they age. In most countries, neurodegenerative diseases are generally recognized as the number one cause afflicting the elderly. Endoplasmic reticulum (ER) stress has been suggested to be associated with some human neurological diseases, such as PD and AD. Melatonin, a neuroendocrine hormone mainly synthesized in the pineal gland, is involved in pleiotropically biological functions, including the control of the circadian rhythm, immune enhancement, and antioxidant, anti-aging, and anti-tumor effects. Although there are many papers on the prevention or suppression of diseases by melatonin, there are very few papers about the effects of melatonin on ER stress in neurons and neurodegenerative diseases. This paper aims to summarize and present the effects of melatonin reported so far, focusing on its effects on neurons and neurodegenerative diseases related to ER stress. Studies have shown that the primary target molecule of ER stress for melatonin is CHOP, and PERK and GRP78/BiP are the secondary target molecules. Therefore, melatonin is crucial in protecting neurons and treating neurodegeneration against ER stress.
Topics: Humans; Aged; Melatonin; Neurodegenerative Diseases; Endoplasmic Reticulum Stress; Antioxidants; Alzheimer Disease; Parkinson Disease; Endoplasmic Reticulum Chaperone BiP
PubMed: 36768703
DOI: 10.3390/ijms24032381 -
Mini Reviews in Medicinal Chemistry 2024Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types... (Review)
Review
Oxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types of cancer, and diabetes. Therefore, finding strategies to detoxify free radicals is an active area of research. One of these strategies is the use of natural or synthetic antioxidants. In this context, melatonin (MLT) has been proven to possess most of the required characteristics of an efficient antioxidant. In addition, its protection against oxidative stress continues after being metabolized, since its metabolites also exhibit antioxidant capacity. Based on the appealing properties of MLT and its metabolites, various synthetic analogues have been developed to obtain compounds with higher activity and lower side effects. This review addresses recent studies with MLT and related compounds as potential antioxidants.
Topics: Melatonin; Antioxidants; Humans; Oxidative Stress; Animals
PubMed: 37366352
DOI: 10.2174/1389557523666230627140816 -
Life Sciences May 2024Melatonin, a potent antioxidant and free radical scavenger, has been demonstrated to be effective in gynecological conditions and female reproductive cancers. This... (Review)
Review
Melatonin, a potent antioxidant and free radical scavenger, has been demonstrated to be effective in gynecological conditions and female reproductive cancers. This review consolidates the accumulating evidence on melatonin's multifaceted protective effects in different pathological contexts. In gynecological conditions such as endometriosis, polycystic ovary syndrome (PCOS), and uterine leiomyoma, melatonin has shown promising effects in reducing oxidative stress, inflammation, and hormonal imbalances. It inhibits adhesion molecules' production, and potentially mitigates leukocyte adherence and inflammatory responses. Melatonin's regulatory effects on hormone production and insulin sensitivity in PCOS individuals make it a promising candidate for improving oocyte quality and menstrual irregularities. Moreover, melatonin exhibits significant antitumor effects by modulating various signaling pathways, promoting apoptosis, and suppressing metastasis in breast cancers and gynecological cancers, including ovarian, endometrial, and cervical cancers. Furthermore, melatonin's protective effects are suggested to be mediated by interactions with its receptors, estrogen receptors and other nuclear receptors. The regulation of clock-related genes and circadian clock systems may also contribute to its inhibitory effects on cancer cell growth. However, more comprehensive research is warranted to fully elucidate the underlying molecular mechanisms and establish melatonin as a potential therapeutic agent for these conditions.
Topics: Humans; Female; Melatonin; Polycystic Ovary Syndrome; Antioxidants; Oxidative Stress; Breast Neoplasms
PubMed: 38479596
DOI: 10.1016/j.lfs.2024.122557 -
Sleep Medicine Reviews Aug 2023Sleep initiation and maintenance problems are common in the pediatric population and while behavioral interventions are recommended, their efficacy remains to be... (Meta-Analysis)
Meta-Analysis Review
Sleep initiation and maintenance problems are common in the pediatric population and while behavioral interventions are recommended, their efficacy remains to be evaluated in clinical trials. We conducted a systematic review and network meta-analysis to assess the efficacy of non-pharmacological treatments and melatonin for sleep initiation and maintenance problems in healthy pediatric populations. We included 30 studies in the systematic review and 15 in the meta-analysis. Three network meta-analyses were conducted for sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time (TST). For SOL variable, the results support greater effectiveness of light therapy and melatonin than evidence-based psychological interventions, whether implemented in combination with light therapy or not. Regarding WASO variable, evidence-based psychological interventions and a combination of those techniques plus light treatment were the most efficacious. Finally, for TST variable, a larger effect was shown for the combined treatment of evidence-based psychological intervention with light therapy in comparison to other interventions. In conclusion, we found a high variability between study protocols likely impacting the results of the meta-analysis. Future randomized control trials studies, stratified by pediatric age classes, are needed in order to provide clear suggestions in clinical settings.
Topics: Humans; Child; Melatonin; Network Meta-Analysis; Sleep; Sleep Initiation and Maintenance Disorders; Cognitive Behavioral Therapy
PubMed: 37406497
DOI: 10.1016/j.smrv.2023.101806 -
Current Medicinal Chemistry 2023Melatonin, mainly released from the pineal gland, also produced in the reproductive organs and cells, plays important roles in rhythms of the sleep-wake cycle,... (Review)
Review
Melatonin, mainly released from the pineal gland, also produced in the reproductive organs and cells, plays important roles in rhythms of the sleep-wake cycle, retardation of ageing processes, and antioxidant/anti-inflammatory functions. As a key mediator in reproductive systems, melatonin is participated in the reproductive process via regulating gamete and embryo development and influences reproductive diseases and pregnancy outcomes. The underlying mechanisms include epigenetic and other regulations, which are interesting for exploring new targets in the prevention and treatment of reproductive diseases. This review discusses the relationship between melatonin and reproductive functions and dysfunction, as well as potential clinical applications of melatonin in reproductive medicine. Notably, Developmental Origins of Health and Diseases (DOHaD) is closely linked to reproduction, this article is the first to review the new progress in studies on the possible relationship between melatonin and DOHaD.
Topics: Pregnancy; Female; Humans; Melatonin; Pineal Gland; Reproduction; Antioxidants; Reproductive Medicine; Circadian Rhythm
PubMed: 36200146
DOI: 10.2174/0929867329666221005101031 -
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 -
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 -
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 -
British Journal of Pharmacology Aug 2018Melatonin, discovered in 1958 in the bovine pineal tissue, is an indoleamine that modulates circadian rhythms and has a wide variety of other functions. Haematological... (Review)
Review
Melatonin, discovered in 1958 in the bovine pineal tissue, is an indoleamine that modulates circadian rhythms and has a wide variety of other functions. Haematological neoplasms are the leading cause of death in children and adolescents throughout the world. Research has demonstrated that melatonin is a low-toxicity protective molecule against experimental haematological neoplasms, but the mechanisms remain poorly defined. Here, we provide an introduction to haematological neoplasms and melatonin, especially as they relate to the actions of melatonin on haematological carcinogenesis. Secondly, we summarize what is known about the mechanisms of action of melatonin in the haematological system, including its pro-apoptotic, pro-oxidative, anti-proliferative and immunomodulatory actions. Thirdly, we discuss the advantages of melatonin in combination with other drugs against haematological malignancy, as well as its other benefits on the haematological system. Finally, we summarize the findings that are contrary to the suppressive effects of melatonin on cancers of haematological origin. We hope that this information will be helpful in the design of studies related to the therapeutic efficacy of melatonin in haematological neoplasms. LINKED ARTICLES: 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; Antineoplastic Agents; Hematologic Neoplasms; Humans; Melatonin
PubMed: 28880375
DOI: 10.1111/bph.13966 -
European Heart Journal. Cardiovascular... Oct 2016Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release... (Review)
Review
Melatonin, widely used to counter transatlantic travel jet lag and insomnia, is synthesized in the suprachiasmatic nucleus of the anterior pituitary gland. Its release into the circulation is stimulated by the onset of darkness, followed by a progressive decrease in blood levels with the onset of dawn. Melatonin administration can maintain the quality of sleep and help to counteract age-induced cognitive decline. Melatonin can also limit the severity of a variety of cardiovascular and cerebrovascular diseases, diabetes, and cancer.
Topics: Animals; Antioxidants; Coronary Disease; Humans; Melatonin
PubMed: 27533945
DOI: 10.1093/ehjcvp/pvv037