Molecular circadian clocks align daily behavioral and metabolic rhythms with the external day-night cycle. Priming energy metabolism for recurring changes on a 24-hour basis, these clocks are deeply interlinked with metabolic homeostasis and health.
Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.
Pancreatic cancer has a high mortality rate due to the absence of early symptoms and subsequent late diagnosis; additionally, pancreatic cancer has a high resistance to radio- and chemotherapy. Multiple inflammatory pathways are involved in the pathophysiology of pancreatic cancer.
Melatonin and pancreatic cancer: Current knowledge and future perspectives. Read More »
Non-small-cell lung cancer (NSCLC) is a type of malignancy with progressive metastasis having poor prognosis and lowered survival resulting from late diagnosis. The therapeutic approaches for the treatment of this incurable cancer are chemo- and radiotherapy.
Melatonin and non-small cell lung cancer: new insights into signaling pathways. Read More »
Sleep inertia, broadly defined as decrements in performance and lowering of alertness following waking, lasts for durations ranging between 1 min and 3 hrs. This study investigated whether, compared to a dim light condition (the control), exposure to long-wavelength (red) light delivered to closed eyelids during sleep (red light mask) and to eyes open upon waking (red light goggles) reduced sleep inertia.
Effects of red light on sleep inertia. Read More »
Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother’s circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus.
The risk of herpes zoster (HZ) increases with age and declining immune function. Increased oxidative stress and inflammatory conditions may cause a negative impact on the immune responses.
Ovarian cancer is one of the most common causes of morbidity related to gynecologic malignancies. Possible risk factors are including hereditary ovarian cancer, obesity, diabetes mellitus, alcohol consumption, aging, and smoking.
Melatonin is a potential inhibitor of ovarian cancer: molecular aspects. Read More »
The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag – a measure of circadian misalignment – with oxidative stress markers.
Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes in the immune system, a deteriorating circadian system, and reductions in sirtuin-1 (SIRT1) activity.
Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks. Read More »
Disruption of circadian rhythmicity induced by prolonged light exposure, altered sleep patterns and shift work is associated with the development of obesity and related metabolic disorders, including type 2 diabetes and cardiovascular diseases.
Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality.
Circadian clocks and insulin resistance. Read More »
Previous research has identified insomnia as a predictor for the onset of depression. The aim of this meta-analysis is to investigate whether insomnia also predicts the onset of other mental disorders.
Insomnia as a predictor of mental disorders: A systematic review and meta-analysis. Read More »
This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00-12:00 hours), afternoon (12:00-18:00 hours), evening (18:00-24:00 hours), and night (24:00-06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT).
Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy.
Melatonin is a lipophilic hormone synthesized and secreted mainly in the pineal gland, acting as a neuroendocrine transducer of photoperiodic information during the night. In addition to this activity, melatonin has shown an antioxidant function and a key role as regulator of physiological processes related to human reproduction.
From Implantation to Birth: Insight into Molecular Melatonin Functions. Read More »
Heart failure is a multifactorial clinical syndrome characterized by the inability of the heart to pump sufficient blood to the body. Despite recent advances in medical management, poor outcomes in patients with heart failure remain very high. This highlights a need for novel paradigms for effective, preventive and curative strategies.
Melatonin in Heart Failure: A Promising Therapeutic Strategy? Read More »
There is considerable evidence that melatonin may be of use in the prevention and treatment of cancer. This manuscript will review some of the human, animal and cellular studies that provide evidence that melatonin has oncostatic properties.
Mechanisms Underlying Tumor Suppressive Properties of Melatonin. Read More »
Oxidative damage to DNA has important implications for human health and has been identified as a key factor in the onset and development of numerous diseases. Thus, it is evident that preventing DNA from oxidative damage is crucial for humans and for any living organism. Melatonin is an astonishingly versatile molecule in this context.
Melatonin: A Versatile Protector against Oxidative DNA Damage. Read More »
Melatonin is an ancient antioxidant. After its initial development in bacteria, it has been retained throughout evolution such that it may be or may have been present in every species that have existed. Even though it has been maintained throughout evolution during the diversification of species, melatonin’s chemical structure has never changed; thus, the melatonin
Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Read More »
Oxidative stress is known as a major contributing factor involved in oocyte aging, which negatively affects oocyte quality and development after fertilization. Melatonin is an effective free radical scavenger and its metabolites AFMK and AMK are powerful detoxifiers that eliminate free radicals.
Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients.
Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality.
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth.
What are the underlying mechanisms of the decline in the fertilization ability of post-ovulatory aged oocytes?
Assisted reproductive technologies (ART) have experienced growing interest from infertile patients seeking to become pregnant. The quality of oocytes plays a pivotal role in determining ART outcomes.
How to Achieve High-Quality Oocytes? The Key Role of Myo-Inositol and Melatonin. Read More »
Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF).
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.
Melatonin as an antioxidant: under promises but over delivers. Read More »
The physiology of oocyte in vitro maturation remains elusive. Generally, the oocytes have a very low maturation rate under in vitro conditions.
Melatonin, an indolamine secreted by the pineal gland, is known as a powerful free-radical scavenger and wide-spectrum antioxidant.
The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs.
Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system.
Evaluating the effectiveness of melatonin in prevention of radiation-induced oral mucositis.
There is currently an urgent need for a viable, cheap, and readily available treatment for the Ebola virus outbreak in West Africa. Here, it is proposed that melatonin may have significant utility in helping the management of this outbreak.
Ebola virus: melatonin as a readily available treatment option. Read More »
The purpose of this article was to summarize what is known about the function of melatonin in the oral cavity.
Melatonin in the oral cavity: physiological and pathological implications. Read More »
Melatonin is a hormone secreted by the enigmatic pineal gland in response to darkness, hence the name hormone of darkness. It has generated a great deal of interest as a therapeutic modality for various diseases particularly sleep disorders.
Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment. Read More »
The purpose of this report is to emphasize the potential utility for the use of melatonin in the treatment of individuals who are infected with the Ebola virus.
Ebola virus disease: potential use of melatonin as a treatment. Read More »
The aim of this study was to evaluate the efficacy of oral melatonin supplementation on oocyte and embryo quality in patients in an assisted reproductive technologies program.
Infertility is the problem of 15% of young couples in different societies. One of the factors that could affect fertility is oxidative stress. Therefore, the aim of the present study is to investigate the level of Melatonin, a free radical scavenger, and its correlation with oxidative biomarkers in infertile men.
Melatonin, a versatile molecule, is synthesized by the pineal gland but also by other organs, including gastrointestinal tract, retina, thymus, bone marrow, and by leukocytes.
Melatonin: its possible role in the management of viral infections – a brief review. Read More »
Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent.
Peripheral reproductive organ health and melatonin: ready for prime time. Read More »
The reactions of N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK) and N(1) -acetyl-5-methoxykynuramine (AMK) with (•) OH, (•) OOH, and •OOCCl3 radicals have been studied using the density functional theory.
On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. Read More »
Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system.
Melatonin: buffering the immune system. Read More »
The quality of metaphase II oocytes deteriorates rapidly following ovulation as the result of an aging process associated with impaired fertilizing potential, disrupted developmental competence, and increased likelihood of embryonic resorption.
Melatonin (N-acetyl-5-methoxytryptamine) is a multifunctional signaling molecule that has a variety of important functions. Numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine.
The aim of the study was to evaluate the efficacy of melatonin administration on oocyte quality in women underwent in vitro fertilization (IVF) cycles.
The efficacy of melatonin administration on oocyte quality. Read More »
Melatonin (N-acetyl-5-methoxytryptamine) is secreted during the dark hours at night by pineal gland, and it regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction.
The role of melatonin as an antioxidant in the follicle. Read More »
Melatonin is a versatile molecule, synthesized not only by the pineal gland, but also in small amounts by many other organs like retina, gastrointestinal tract, thymus, bone marrow, lymphocytes etc.
Melatonin in bacterial and viral infections with focus on sepsis: a review. Read More »
The purpose of this study was to evaluate the association between the follicular fluid (FF) reactive oxygen species (ROS) levels, total antioxidant capacity (TAC) and ROS-TAC score and pregnancy after intracytoplasmic sperm injection (ICSI).
The main objective of this study was to detect fatigue-induced clinical symptoms of immune suppression in medical residents. Samples were collected from the subjects at rest, following the first night (low-stress), and the last night (high-stress) of night float.
Fatigue in medical residents leads to reactivation of herpes virus latency. Read More »
Bisphenol A (BPA) is a monomer of polycarbonate plastic used to manufacture plastic baby bottles and lining of food cans. It has endocrine-disrupting potential and exerts both toxic and estrogenic effects on mammalian cells.
This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation.
Protective role of melatonin in progesterone production by human luteal cells. Read More »
We aimed to analyse the in vitro fertilization-embryo transfer (IVF-ET) outcomes of the patients with sleep disturbances who were administered melatonin.
A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder. Obesity and the associated health problems urgently require effective strategies of treatment.
Although human seminal fluid contains melatonin and spermatozoa reportedly possess membrane melatonin receptors, there are no experimental studies that have ascertained the relationship between melatonin and male infertility.
A recent prospective study indicated that melatonin supplements may reduce the progression of idiopathic scoliosis, the most common deformity of the spine. This form of scoliosis occurs during rapid skeletal growth.
Melatonin is a versatile molecule, synthesized not only in the pineal gland, but also in many other organs. Melatonin plays an important physiologic role in sleep and circadian rhythm regulation, immunoregulation, antioxidant and mitochondrial-protective functions, reproductive control, and regulation of mood.
Melatonin in septic shock: some recent concepts. Read More »
During the last 20 years, numerous clinical trials have examined the therapeutic usefulness of melatonin in different fields of medicine. The objective of this article is to review, in depth, the science regarding clinical trials performed to date.
Clinical uses of melatonin: evaluation of human trials. Read More »
Melatonin (N-acetyl-5-methoxytryptamine) has revealed itself as an ubiquitously distributed and functionally diverse molecule. The mechanisms that control its synthesis within the pineal gland have been well characterized and the retinal and biological clock processes that modulate the circadian production of melatonin in the pineal gland are rapidly being unravelled.
Melatonin: a multitasking molecule. Read More »
Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses.
Melatonin: a pleiotropic molecule regulating inflammation. Read More »
It is commonly accepted that melatonin (N-acetyl-5-methoxytryptamine), the most relevant pineal secretory product, has oncostatic properties in a wide variety of tumors and, especially, in those identified as being hormonedependent.
Basic mechanisms involved in the anti-cancer effects of melatonin. Read More »
This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases.
Melatonin: action as antioxidant and potential applications in human disease and aging. Read More »
Besides its well-known regulatory role on circadian rhythm, the pineal gland hormone melatonin has other biological functions and a distinct metabolism in various cell types and peripheral tissues. In different tissues and organs, melatonin has been described to act as a paracrine and also as an intracrine and autocrine agent with overall homeostatic functions and pleiotropic effects that include cell protection and prosurvival factor.
Melatonin signaling and cell protection function. Read More »
Pancreatic cancer is a highly lethal disease with a poor prognosis for long-term survival rate at all stages of invasiveness. It responds poorly to radio- and chemotherapy because the tumor cells are resistant to apoptosis.
It is assumed somatic cells can die in the apoptotic, the autophagic, or the necrotic way; however, the mechanisms of sperm death are not clear.
The objective of this paper was to analyze the data supporting the possible role of melatonin on bone metabolism and its repercussion in the etiology and treatment of bone pathologies such as the osteoporosis and the adolescent idiopathic scoliosis (AIS). Melatonin may prevent bone degradation and promote bone formation through mechanisms involving both melatonin receptor-mediated and receptor-independent actions.
The aim of the study was to evaluate the efficacy of a treatment with myo-inositol plus folic acid plus melatonin compared with myo-inositol plus folic acid alone on oocyte quality in women underwent in vitro fertilization (IVF) cycles.
The experimental data obtained from both human and rodent studies suggest that melatonin may have utility in the treatment of several cardiovascular conditions. In particular, melatonin’s use in reducing the severity of essential hypertension should be more widely considered. In rodent studies melatonin has been shown to be highly effective in limiting abnormal cardiac physiology and the loss of critical heart tissue resulting from ischemia/reperfusion injury.
Beneficial effects of melatonin in cardiovascular disease. Read More »
Various systems of antioxidants exist endogenously in the body to help protect it against free radical damage by scavenging excessive ROS and RNS.
Objectives of this study were to investigate the effects of prolonged-release melatonin 2 mg (PRM) on sleep and subsequent daytime psychomotor performance in patients aged > or =55 years with primary insomnia, as defined by fourth revision of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association.
To summarize the role of melatonin in the physiology and pathophysiology of the ovary.
Melatonin and the ovary: physiological and pathophysiological implications. Read More »
Melatonin, a widespread hormone in the animal kingdom, is produced by several organs and tissues besides the pineal gland. Whilst extrapineal melatonin behaves as a cytoprotective molecule, the pineal produces the hormone in a rhythmic manner. The discovery of melatonin in 1958, and the characterization of its synthesis somewhat later, let to the description of its photoperiodic regulation and its relationship with the biological rhythms such as the sleep/wake rhythm.
Melatonin, synthetic analogs, and the sleep/wake rhythm. Read More »
The aim of this study was to investigate the effects of exogenous melatonin on sleep-wake rhythm in haemodialysis patients.
Sleep duration has been hypothesized to be inversely associated with breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. However, data are inconclusive from the three studies conducted in Western populations on sleep duration and breast cancer risk.
Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Read More »
Low urinary melatonin levels have been associated with an increased risk of breast cancer in premenopausal women. However, the association between melatonin levels and breast cancer risk in postmenopausal women remains unclear.
Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. Read More »
Mercury is one of the most investigated natural elements and potential contaminants in the environment. Antioxidants have long been known to reduce the free radical-induced oxidative damage.
Infection with Herpes simplex virus type 1 (HSV-1) typically causes lesions of the mouth, face, skin, esophagus, or brain. Herpes simplex virus type 2 (HSV-2) usually causes infections of the genitals, rectum, skin, hands, or meninges.
We investigated the relationship between oxidative stress and poor oocyte quality and whether the antioxidant melatonin improves oocyte quality.
Melatonin is known to inhibit insulin secretion from rodent beta-cells through interactions with cell-surface MT1 and/or MT2 receptors, but the function of this hormone in human islets of Langerhans is not known.
Function and expression of melatonin receptors on human pancreatic islets. Read More »
Melatonin influences insulin secretion both in vivo and in vitro.
Melatonin, endocrine pancreas and diabetes. Read More »
The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals.
Role of the melatonin system in the control of sleep: therapeutic implications. Read More »
The circadian release of the hormone melatonin is regulated by the suprachiasmatic nucleus (SCN), which feeds back into the nucleus to modulate sleep and circadian phase through activation of the MT(1) and/or MT(2) melatonin receptors.
Melatonin receptors: role on sleep and circadian rhythm regulation. Read More »
To determine the effects of sleep and sleep deprivation on plasma melatonin concentrations in humans and whether these effects are age-dependent.
Melatonin is a highly conserved molecule. Its presence can be traced back to ancient photosynthetic prokaryotes. A primitive and primary function of melatonin is that it acts as a receptor-independent free radical scavenger and a broad-spectrum antioxidant.
Pineal melatonin regulates circadian rhythms and influences sleep. Melatonin also has protective actions against tissue damage from free-radicals and other toxins.
Evidence supporting the use of melatonin in short gestation infants. Read More »
Cadmium (Cd) is a heavy metal affecting human health both through environmental and occupational exposure. There is evidence that Cd accumulates in several organs and is carcinogenic to humans.
There are functional inter-relationships between the beta cells of the endocrine pancreas and the pineal gland, where the synchronizing circadian molecule melatonin originates. The aim of this study was to elucidate a putative interaction between insulin and melatonin in diabetic patients and a diabetic rat model.
To determine if melatonin improves tinnitus and if this improvement is related to improvement in sleep.
The effects of melatonin on tinnitus and sleep. Read More »
Delayed sleep phase syndrome (DSPS) is a circadian-rhythm sleep disorder characterized by abnormally late sleep and wake times. Melatonin, taken in the evening, advances sleep and circadian phase in patients with DSPS. However, little is known about the most effective dose or time of administration. In the present study, we tested the effectiveness of melatonin to advance the timing of sleep and circadian phase in individuals with DSPS.
Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Read More »
The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics.
Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy. Read More »
This double-blind, randomized, placebo-controlled study in epileptic children, aged 3 to 12 years, evaluated the effect of add-on melatonin on the sleep behavior of these children on sodium valproate monotherapy using a parental questionnaire.
To summarize the role of melatonin and circadian rhythms in determining optimal female reproductive physiology, especially at the peripheral level.
Melatonin and the circadian system: contributions to successful female reproduction. Read More »
In addition to the well-known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far.
Recent data suggest that melatonin may influence human physiology, including the sleep-wake cycle, in a time-dependent manner via the body’s internal clock.
Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. Read More »
In numerous experimental systems, the neurohormone melatonin has been shown to protect against oxidative stress, an effect which appears to be the result of a combination of different actions. In this study, we have investigated the possible contribution to radical scavenging by substituted kynuramines formed from melatonin via pyrrole ring cleavage.
Previously, we reported that morning bright light therapy improved sleep time and cognitive function in Alzheimer type of dementia.
This review summarizes the numerous reports that have documented the neuroprotective actions of melatonin in experimental models of ischemia/reperfusion injury (stroke).
In both permanent and transient 3-hour middle cerebral artery occlusion rat stroke models, a single intraperitoneal injection of melatonin at 5 or 15 mg/kg given before ischemia was shown to reduce infarct volume at 72 hours. The present study was conducted to examine the treatment time window when melatonin was commenced after onset of ischemia.
In this paper we review the historical milestones that first highlighted the existence of a relationship between melatonin and the immune system and we summarize data from experiments which correlate the rhythmic production of melatonin with the rhythmic activity of the immune system.
Melatonin-immune system relationships. Read More »
Free radicals have been implicated in the pathogenesis of neonatal sepsis and its complications.
Effects of melatonin treatment in septic newborns. Read More »