Importance Of Melatonin Research Articles

The history of circadian rhythm research in Austria.

In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich and pioneering history of circadian research in Austria. Among the forefathers of circadian research in Vienna are Otto Marburg (1874-1948), who discovered important elements of the pineal gland physiology, Robert Hofstätter (1883-1970), who used pineal gland extract in obstetrics/gynecology, and Paul Engel (1907-1997), who discovered that the pineal gland was controlled by light. More recently, Vera Lapin (1920-2007) showed that surgical removal of the pineal gland increased tumor growth, while Franz Waldhauser (*1946) investigated melatonin in conjunction with night work. Michael Kundi (*1950) and his team conducted among the first studies demonstrating differences in rhythms of night workers and early evidence for health impairments among them. Furthermore, Vienna-born Erhard Haus (1926-2013) pioneered the discovery of the role and importance of melatonin in relation to numerous diseases. This rich pioneering contribution of scientists in Vienna or with roots in Vienna is continued today by anew generation of chronobiologists, epidemiologists and clinicians in Vienna whose new insights contribute to the rapidly developing field of circadian rhythms research. Current topics and contributions relate to the impact of circadian rhythm disruption on health, and the application of chronotherapeutic approaches in clinical and preventive settings.

Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool.

Infertility is an increasing global public health concern with socio-psychological implications for affected couples. Remarkable advances in reproductive medicine have led to successful treatments such as assisted reproductive techniques (ART). However, the search for new therapeutic tools to improve ART success rates has become a research hotspot. In the last few years, pineal indolamine melatonin has been investigated for its powerful antioxidant properties and its role in reproductive physiology. It is considered a promising therapeutical agent to counteract the detrimental effects associated with oxidative stress in fertility treatments. The aim of the present narrative review was to summarize the current state of the art on the importance of melatonin in reproductive physiology and to provide a critical evaluation of the data available encompassing basic, translational and clinical studies on its potential use in ART to improve fertility success rates.

Investigation of relationship between melatonin level and religious orientation, depression level and sleep quality of students in nursing and different department

Background. With insufficient information about the importance of melatonin in human physiology, this hormone is known to be associated with sleep, mood, reproduction, tumor development, and aging. Chronic sleep problems, stress, fatigue, irritability, confusion, tension, and depressive symptoms can be observed in melatonin deficiency. There is no such study in the literature and it is thought to shed light on the literature. The purpose of the study is to examine the relationship between melatonin level and religious orientation, depression level, and sleep quality of students in nursing and different department. Materials and methods. This cross-sectional study was conducted between April 2019 and April 2020. The target population of the study consisted of 1200 students who studying in 2nd grade to ensure harmony and homogeneity in stress, sleep, and melatonin parameters. The sample of the study consisted of 145 individuals who accepted to participate in the study among the 2nd-grade students. Descriptive Information Form, Religious Orientation Scale, Beck Depression Inventory, and Pittsburg Sleep Quality Index (PSQI) scale were used to collect research data. Results. According to the findings obtained from the study, it was determined that the melatonin level of the students was 0.79±0.52 pg/ml, the total score mean of the Sleep Quality Scale was 7.24±3.35, the Beck Depression Inventory was 16.40±10.84 and the Religious Orientation Scale was 47.41±6.05. It was determined that their sleep quality was “bad”; moderately depressed and religious orientation and the melatonin level was below normal. Conclusions. Since the sleep quality total score of the students was above 5, it was determined that their sleep quality was “bad”. It was found that the group was moderately depressed and had a moderate religious orientation. In the study where the standard was accepted as 0.90, it was found that the melatonin level was below normal. It is recommended that the study be conducted in larger groups.

Gut Microbiota Mediate Melatonin Signaling in Association With Type 2 Diabetes

ObjectivesTo investigate the association between serum melatonin (MT) and type 2 diabetes (T2D) risk in southern Chinese population in a case-control study as well as the role of gut microbiota in the relationship between them.MethodsT2D cases and healthy controls (n = 2034) were recruited from a cross-sectional study and matched age and sex for a case-control study, and the association between serum MT and T2D risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n = 120), in which gut microbial 16S RNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach.ResultsHigher levels of serum MT were significantly associated with a lower risk of T2D (OR = 0.84; 95% CI 0.75–0.93) and with lower levels of fasting glucose after adjustment for covariates (β = −0.21; 95% CI −0.33, −0.09). T2D patients exhibited lower levels of serum MT, lower α- and β-diversity of gut microbiota (p < 0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (LDA > 2.0). Seven genera were correlated with MT and T2D related traits, among them Bifidobacterium was positively correlated with serum LPS and IL-10, whereas Coprococcus was negatively correlated with serum IL-1β, IL-6, IL-10, IL-17, INF-α and LPS (FDR < 0.05). Moreover, altered metabolites were detected in the T2D patients, and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR < 0.05). A significant correlation also was found between Trp metabolites and inflammation factors, such as IL-1β, IL-6, IL-10, IL-17, INF-α and LPS (FDR < 0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict T2D status (AUC = 0.804).ConclusionsHigher level of serum MT was associated with lower risk of T2D, and that gut microbiota-mediated MT signaling was involved in this association, especially, Bifidobacterium and Coprococcus mediated Trp metabolites may be involved in the process. These findings uncover the importance of MT and MT-related bacteria and metabolites as potential therapeutic targets for T2D.Funding SourcesThis work was supported by the National Natural Science Foundation of China (No.82060593), Natural Science Foundation of Guangxi Province (No. 2018GXNSFDA050019).

Aqueous solvation study of melatonin using ab initio molecular dynamics

Melatonin is an essential human hormone produced mainly by the pineal gland from the amino acid tryptophan; it has several types of bioactivity, such as regulation of circadian rhythm, antioxidant, and DNA protection. Despite the importance of melatonin in the human body, studies on the interaction of melatonin with water molecules, considered explicitly, are quite limited in the literature. Thus, the present work reports a study on the effects of aqueous solvation on the geometric and electronic parameters of melatonin using Car-Parrinello Molecular Dynamics (CPMD). The CPMD results show that the aqueous solvation of melatonin affects mainly C14-O2 (2.176%), N17-C14 (2.169%), and N16-H21 (1.079%) bond lengths as well as O1-C3-C4 (4.37%) and O1-C3-C8 (4.241%) bond angles. These effects are attributed mainly to the H-bond formation between O1, O2, H21, and H30 melatonin sites and water molecules. The topological analysis of the H-bond electron density shows that the H-bond strength varies from weak to intermediate intensities, except for the O2 site – where it varies from weak to strong. The energetic aspect of the H-bonds was investigated using Helmholtz free energy, and the radial distribution function was employed to assess the mean residence time of the water atoms inside the first shell. The supramolecular arrangement of melatonin in the solid-state was investigated using the Hirshfeld surface technique. These findings deepen the knowledge of melatonin chemistry in the human body and help develop explanations for its biological activities.

Role of Melatonin in Angiotensin and Aging.

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.

The importance of melatonin in the regulation of metabolism, eating behavior, sleep, and the prospects for the use of melatonin drugs for obesity treatment

Melatonin is a special hormone that act as an internal synchronizer of circadian rhythms, the organism physiology and behavior to the environmental day and night and seasons of the year. The present urban society and the industrial production processes as organized should be considered, as both depend on the presence of indoor lights during the night and include the profuse use of electronic devices whose screens are rich in blue wavelength light. Light during the night delays the beginning of the secretory episode of melatonin and blunts its peak, causing chronic hypomelatoninemia. Hypomelatonemia, that causes deprivation of sleep and eating behavior disorders, along with low physical activity, can be the reason of the obesity, «non-infectious epidemic of the 21st century». According to this, the use of melatonin drugs for obesity treatment can be effective. Further prospective, controlled, randomized trials in this area are required to confirm this hypothesis.

Pharmacological agents under investigation in the treatment of coronavirus disease 2019 and the importance of melatonin.

Coronavirus disease 2019 (COVID‐19) is a life‐threatening infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). COVID‐19 pandemic causing morbidities and even deaths worldwide revealed that there is urgent need to find pharmacological agents or vaccines. Although there are a lot of agents under investigation, there is no approved agent for the prevention or treatment of the COVID‐19 yet. Treatment of patients remains mainly supportive as well as compassionate use of the agents under investigation. It is well established that excessive inflammatory and immune response and oxidative injury play a critical role in the pathogenesis of COVID‐19. In this review, we aimed to update knowledge about pathogenesis, clinical features, and pharmacological treatment of COVID‐19 and review the potential beneficial effects of ancient antioxidant, anti‐inflammatory, and immunomodulatory molecule melatonin for prevention and treatment of COVID‐19.

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light–dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer’s and Parkinson’s disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.

Melatonin-mediated regulation of autophagy: Making sense of double-edged sword in cancer.

Much research has been conducted to discover novel techniques to reverse the process of tumorigenesis and, cure already stablished malignancies. One well-stablished approach has been the use of organic compounds and naturally found agents such as melatonin whose anticancer effects have been shown in multiple studies, signaling a unique opportunity regarding cancer prevention and treatment. Various agents use a variety of methods to exert their anticancer effects. Two of the most important of these methods are interfering with cell signaling pathways and changing cellular functions, such as autophagy, which is essential in maintaining cellular stability against multiple exogenous and endogenous sources of stress, and is a major tool to evade early cell death. In this study, the importance of melatonin and autophagy are discussed, and the effects of melatonin on autophagy, and its contribution in the process of tumorigenesis are then noted.

Melatonin in macrophage biology: Current understanding and future perspectives.

Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage-associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF-κB, STATs, and NLRP3/caspase-1. Notably, miRNAs (eg, miR-155/-34a/-23a), cellular metabolic pathways (eg, α-KG, HIF-1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage-associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage-associated diseases.

Assessment of the serum level of melatonin and its correlation with insulin, insulin resistance, and glycated hemoglobin in Iraqi patients with polycystic ovarian syndrome

Background: Polycystic ovarian syndrome (PCOS) is one of the most frequent gynecological endocrinopathy that occur in premenopausal females. The importance of melatonin (N-acetyl-5-methoxytryptamine) in human reproduction is still unidentified. A numerous study suggests that melatonin and reproductive hormones are closely related. Objectives: The study aimed to evaluate the role of melatonin in women with PCOS and its correlation with insulin, insulin resistance (IR), and glycated hemoglobin (HbA1c) in a patient with PCOS. Materials and Methods: A prospective cross-sectional study was designed taking 60 PCOS patients and 30 controls women from January to April 2019. These patients admitted to obstetrics and gynecology unit at Babylon teaching hospital. Five milliliter of blood sample was taken on day 2 of menstrual cycle from each subject enrolled in this study. Blood samples were collected for testing serum melatonin, insulin, IR, and HbA1c estimation. Results: The study showed that there is the significant difference between PCOS women and the control group concerning melatonin level. Results also showed higher means of HbA1c in PCOS women than control women, and positive correlation between HbA1c and melatonin. The study showed higher means of insulin was shown in PCOS women when compared with control group, and positive correlation between insulin and melatonin. Furthermore, this study showed higher means of IR was recorded in PCOS women when compared with control group, and positive correlation between IR and melatonin. Conclusions: Women with PCOS have significant increase of serum melatonin in PCOS women. And, there were significant increases in serum levels of HbA1c, insulin, and IR in women with PCOS compared to healthy women. In addition, positive correlation was found between melatonin with insulin, IR, and HbA1c. This study could open the way for therapeutic role of melatonin in the treatment of PCOS women.

Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin's roles in prophylaxis and management.

Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on carbohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the “prophylaxis” or management of diabetes mellitus is also considered.

Melatonin in plant morphogenesis

Melatonin is a ubiquitously present indoleamine with a vast capacity for modulating the growth and behavior of plants, animals, and microbes. Though melatonin was discovered in plants decades after its discovery in mammals, its presence has now been confirmed in almost all plant families. Despite this, the in vitro and in vivo mechanisms of action of melatonin are still poorly defined. Although there are an increasingly large number of investigations into the roles of melatonin in plants, few take advantage of in vitro culture systems. Melatonin has been found to possess several important roles in plant growth and development, including functions in rhythmic and cyclic processes, such as chronoregulation, seasonal and senescence processes, as well as modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, and responses to biotic and abiotic stresses. This review highlights the potential for use of melatonin in several in vitro systems, the roles it plays in plant morphogenesis, and the importance of melatonin in communication within and between plants, and how in vitro systems can be exploited to better understand these understudied functions of melatonin.

The Importance of Melatonin and Mitochondria Interaction in Mood Disorders and Schizophrenia: A Current Assessment.

Mitochondria play a critical role in regulating cellular functions, such as redox signaling, calcium homeostasis, and apoptosis. Also, mitochondria are crucial for neurogenesis and neuronal functions. Melatonin is an indole analog hormone, which is generally produced by the pineal gland. It plays a vital role in circadian rhythm and act as a powerful antioxidant by scavenging free radicals, immunomodulators, and anticancer agents. Schizophrenia and mood disorders are the two major psychiatric disorders. Disturbances of sleep and circadian rhythms are well-known symptoms of schizophrenia and mood disorders (bipolar disorder, major depression). Since melatonin has a regulator effect on circadian rhythm and sleep quality, it has a close interaction with schizophrenia and mood disorders. Herein, we aimed to summarize the effects of melatonin on mitochondrial activity in schizophrenia and mood disorders.

Reproductive phase dependent variation in lung-associated immune system (LAIS) and expression of melatonin receptors (Mel1a and Mel1b) in the lung of the Jungle-Bush Quail (Perdicula asiatica)

The present study was performed to assess the variation of the lung-associated immune system (LAIS) in the Jungle-Bush Quail ( Perdicula asiatica (Latham, 1790)) during two different reproductive phases when differences in the circulatory level of hormones (melatonin and gonadal steroid) and environmental conditions were maximum. We noted high significant variation in size and number of bronchus-associated lymphoid tissue (BALT) nodules, as well as in the size and number of non-BALT nodules, during the reproductively inactive phase (RIP; December) compared with the active phase (RAP; June). We also noted high significant variation in the percent stimulation ratio of lung lymphocyte, as well as in the concentrations of plasma melatonin and melatonin receptors, during RIP compared with RAP. Testosterone level and number of macrophages in lungs were high during RAP. Thus, we suggest that the LAIS had reproductive phase dependent variation, which could be due to (i) variation in environmental factors (photoperiod, temperature, and humidity) and (ii) circulatory level of hormones (melatonin and testosterone). Because of the importance of melatonin in avian immune regulation, we assess and document the expression of melatonin receptor types Mel1a and Mel1b in the avian lung, which suggest that the lung is a target organ for melatonin and that melatonin is an immunomodulator for lung-associated immunity in birds.

Implication of melatonin in oocyte maturation in Indian major carp Catla catla

Importance of melatonin (N-acetyl-5-methoxytryptamine) in the regulation of oocyte maturation has been studied in a carp Catla catla. Melatonin secretory cells were immunocytochemically localized only in the end vesicle. Diurnal and seasonal studies indicated that the serum levels of melatonin exhibit a minimum diurnal value in the mid-day of all seasons, but the peak value is attained either at mid-night or just before the onset of light. Moreover, highest seasonal value of melatonin was noted in the post-spawning phase. Administration of melatonin at different doses (25, 50, or 100 mug/100 g body weight) for 1, 15, or 30 days resulted in either pro- or anti-gonadal effects depending on the reproductive seasons. In vitro study revealed that incubation of oocytes with melatonin 4h prior to addition of MIH in the medium led to an accelerated rate of oocyte maturation through the formation of a complex of two proteins (MPF), cyclin B and cyclin dependant kinase, Cdc2. Moreover, melatonin pre-incubation considerably increased MIH stimulation of histone H1 phosphorylation as compared to MIH alone. Taken together, gathered information promotes the idea of a physiological role of melatonin in the maturation of oocytes in Catla catla.

Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma c6 cells and its mechanism

Astrocytosis is a common feature of amyloid plaques. The Aβ–astrocyte interaction produces a detrimental effect on neurons, which may contribute to neurodegeneration in Alzheimer disease (AD). The regulation of astrocyte apoptosis is essential to physiological and pathological processes in the CNS. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that melatonin alleviated the learning and memory deficits in the APP 695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Aβ-induced apoptosis in an astrocyte-like cell is discussed. We found that rat astroglioma C6 cells treated with Aβ25-35 or Aβ1-42 undergo apoptosis and that melatonin pretreatment at 10 −5, 10 −6, and 10 −7 M significantly attenuates Aβ25-35- or Aβ1-42-induced apoptosis. The antiapoptotic effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including an MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Aβ1-42-induced nitric oxide formation, remarkably prevented Aβ1-40-induced intracellular calcium overload, and significantly alleviated Aβ1-40-induced membrane rigidity. Our results demonstrate that, in addition to the beneficial effects of providing direct antioxidant protection to neurons, melatonin may enhance neuroprotection against Aβ-induced neurotoxicity by promoting the survival of glial cells.

Melatonin reduces amyloid beta-induced apoptosis in pheochromocytoma (PC12) cells.

The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are partly mediated by free radicals has provided insights into the mechanisms of cell death in Alzheimer's disease (AD) and an avenue to explore new therapeutic approaches. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that long-term application of melatonin alleviated the learning and memory deficits in the APP695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Abeta-induced apoptosis was investigated. Rat pheochromocytoma (PC12) cells treated with either Abeta25-35 or Abeta1-42 underwent apoptosis. Melatonin pretreatment at 10(-5), 10(-6) and 10(-7) m significantly attenuated Abeta25-35- or Abeta1-42-induced apoptosis in PC12 cells. The anti-apoptotic effects of melatonin were highly reproducible and corroborated by multiple quantitative methods, including MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Abeta1-42-induced nitric oxide formation, potently prevented Abeta1-40-induced intracellular calcium overload and significantly alleviated Abeta1-40-induced membrane rigidity. These results suggest that the mechanism of Abeta neurotoxicity involves oxidative stress, and the neuroprotective effects of melatonin are, at least in part, associated with its antioxidant properties. The use of melatonin or its derived analogs should be explored as a therapeutic approach in AD.

The effects of different daytime light intensities on the diel patterns of plasma melatonin in fingerling and broodstock rainbow trout (Oncorhynchus mykiss)

Diel plasma melatonin levels were measured to determine the effects of varied light intensities in juvenile and adult rainbow trout. This study showed that night-time melatonin plasma concentrations were significantly higher (P < 0.05) in juveniles (600±75 pg/mL to 492±29 pg/mL) than broodstock (314±3 pg/mL to 265±55 pg/mL) at 1250 lux. Light intensities of 700 lux were unresponsive in both groups. This amplitudinal difference between juvenile and adult fishes response to light may suggest a developmental importance of melatonin.