Exogenous Melatonin Supplementation Research Articles

Meta-analysis of experimental studies of the effect of melatonin monotherapy on the levels of thyroid hormones and glucocorticoids in rats kept under standard condition

Melatonin is known to modulate circadian and seasonal rhythms in metabolism, reproduction, and behavior. However, the effect of exogenous melatonin supplementation on the functioning of the thyroid and adrenal glands in species without a clear seasonality in reproduction is still unclear. Using a meta-analysis of publications, to investigate the effect of melatonin monotherapy on the concentrations of pituitary thyroid-stimulating hormone, thyroid hormones (TG), pituitary adrenocorticotropic hormone and corticosterone (CS) in rats kept under standard laboratory conditions. In our work, using the Review Manager 5.3 program, we conducted a meta-analysis of publications examining the effect of melatonin monotherapy on the functioning of the thyroid gland (22 papers) and adrenal glands (20 papers) in rats kept under standard conditions. According to the results of our meta-analysis, the effects of melatonin on the levels of TG and CS depend on the dose and duration of therapy. A decrease in TG and CS was associated with therapy lasting no more than 4-5 weeks and with high doses of melatonin. An increase in CS and a trend toward increased TG levels were observed with longer therapy. However, a few studies have observed a decrease in TG with very long-term melatonin therapy (≥32 weeks). Among all TGs, total thyroxine (T4) showed maximum sensitivity to exogenous melatonin, which indicates the influence of melatonin on the secretory function of the thyroid gland. In addition, melatonin increased the relative weight of the adrenal glands. There was no convincing evidence that the effects of melatonin were influenced by the route and timing of administration, or the timing of blood sampling. As a result, exogenous melatonin can modulate TG and CS levels, even in species without a clear seasonality in reproductive function.

Coculture of Chlorella protothecoides and Coccomyxa subellipsoidea enhances cell growth and lipid accumulation: An effective strategy for biodiesel production

Microalgae coculture could resist impurities contamination and fulfill many special biosynthetic processes than microalga monoculture, which might be one of the potential strategies in boosting lipid productivity for biodiesel industrialization. This study explored the possibilities of coculturing of Chlorella protothecoides (CP) and Coccomyxa subellipsoidea (CS) in terms of enhanced cell growth and lipid accumulation. Dual-species coculture with a CP:CS inoculation ratio of 3:7 and a carbon/nitrogen (C/N) ratio of 32 achieved a biomass yield of 6.91 g/L and lipid productivity of 1.07 g/L/d, respectively, representing 1.41- to 1.70- and 3.05- to 3.10-fold increases over the values from dual species monoculture. This dual-species consortium also had increased proportions of C16–C18 (>96 %) and C18:1 fatty acid (50.27 %), providing excellent feedstock for biodiesel production. Furthermore, the CP and CS coculture had a shorter 4-day logarithmic growth cycle than either the CP (5-day) or CS (6-day) monoculture alone. Transcriptomic and metabolomic data indicated that CP and CS in dual-species consortium each performed specific tasks: CP increased the carbon sink and decreased lipid β-oxidation, while CS secreted beneficial factors to the extracellular environment to resist contamination with pathogens and stabilize pH fluctuations, thus supporting lipid accumulation. Exogenous metabolite melatonin (50 μM) supplementation further promoted the biomass and lipid content of coculture CP and CS to reach 9.27 g/L and 69.86 %. This mutualistic interaction strategy involving the use of CP and CS to boost lipid productivity could promote development in the industrial field of biodiesel production.

Preharvest melatonin application mitigates arsenic-induced oxidative stress and improves vase life of tuberose (Polianthes tuberosa L.) cut flowers

Arsenic (As) stress severely hinders the growth of ornamental cut flowers. Melatonin (MLT) as a biostimulant protects plants from various abiotic stresses including As stress. However, its protective roles are not well understood in ornamental cut flowers especially tuberose. This research investigated the effects of exogenous melatonin supplementation on alleviating As stress damage in tuberose plants. In As-treated plants, growth traits and leaf chlorophyll contents markedly decreased, while application of MLT, alleviated the inhibitory effect of As on plant growth and chlorophyll content in As-treated plants. Melatonin application considerably increased the vase life of cut tuberose flowers and also improved the protein as well as proline contents in leaf tissues. Level of oxidative markers including electrolyte leakage (EL), malondialdehyde (MDA) and hydrogen peroxide (H2O2) increased in As-treated plants. Upon application of MLT, this trend was alleviated; however, the activities of enzymatic antioxidants increased when plants were subjected to As stress in combination with MLT. Results obtained in the present study suggest that exogenous MLT could alleviate negative effects of As stress on tuberose plants stimulating of oxidative defense related antioxidants. These results are beneficial to improve ornamental tuberose cut flowers production in heavy metal polluted soils or irrigation water.

Melatonin reduced colon inflammation but had no effect on energy metabolism in ageing Mongolian gerbils (Meriones unguiculatus)

In photoperiod-sensitive wild animals, the secretion of melatonin (MT) is modulated by external photoperiod, and MT affects inflammation and the ageing process. The beneficial effects of MT in delaying the progress of ageing have been reported in laboratory mice and rats. However, little is known about MT in wild mammals. In the current study, we investigated energy metabolism, microbial community structure and colon homeostasis in ageing Mongolian gerbils (Meriones unguiculatus) through exogenous supplementation of MT to test the hypothesis that MT has beneficial effects on gut homeostasis in ageing gerbils. Exogenous MT supplementation had no effect on energy metabolism in Mongolian gerbils but reduced the levels of circulating tumor necrosis factor-α (TNF-α), immune globulin G (IgG) and corticosterone (CORT). The increase in the level of inflammation in ageing animals was related to changes in the structure and diversity of the gut microbiota. At the genus level, the relative abundance of Prevotella, Treponema, Corynebacterium, and Sphingomonas was increased in ageing animals and decreased significantly by the treatment of MT. Christensenella and Lactobacillus were attenuated in ageing animals, and tended to be enhanced by MT treatment. Functions related to glycosphingolipid biosynthesis-ganglio series and lipopolysaccharide biosynthesis (metabolisms of cofactors, vitamins and glycan) were increased in ageing animals and decreased significantly by the treatment of MT. Our data suggest that a supplement of MT could improve colon homeostasis through changing the composition of gut microbiota and reducing inflammation in ageing gerbils.

Melatonin Treatment in Kidney Diseases

Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

Melatonin improves the homeostasis of mice gut microbiota rhythm caused by sleep restriction

Insufficient sleep is regarded as a disruptor of circadian rhythm, and it also contributes to the occurrence of intestinal diseases. The physiological functions of the gut depend on the normal circadian rhythm of the intestinal microbiota. However, how lack of sleep affects intestinal circadian homeostasis is unclear. Therefore, we subjected mice to sleep restriction and found that chronic sleep loss disrupts the pattern of colonic microbial communities and reduces the proportion of gut microbiota with a circadian rhythm, with concomitant changes in the peak phase of the KEGG pathway. We then found that exogenous melatonin supplementation restored the proportion of gut microbiota with a circadian rhythm and increased the KEGG pathway with a circadian rhythm. And we screened for possible circadian oscillation families, Muribaculaceae and Lachnospiraceae, that are sensitive to sleep restriction and can be rescued by melatonin. Our results suggest that sleep restriction disrupts the circadian rhythm of the colonic microbiota. In contrast, melatonin ameliorates disturbances in the circadian rhythm homeostasis of the gut microbiota due to sleep restriction.

Melatonin increases susceptibility to atrial fibrillation in obesity via Akt signaling impairment in response to lipid overload.

Melatonin has been proven to have antiarrhythmic potential; however, several studies have recently challenged this view. Herein, using a mouse model of obesity-induced atrial fibrillation (AF), we tentatively explored whether exogenous melatonin supplementation could increase AF susceptibility in the context of obesity. We observed that an 8-week drinking administration of melatonin (60 µg/ml in water) induced a greater susceptibility to AF in obese mice, although obesity-induced structural remodeling was alleviated. An investigation of systemic insulin sensitivity showed that melatonin treatment improved insulin sensitivity in obese mice, whereas it inhibited glucose-stimulated insulin secretion. Notably, melatonin treatment inhibited protein kinase B (Akt) signaling in the atria of obese mice and palmitate-treated neonatal rat cardiomyocytes, thereby providing an AF substrate. Melatonin increased lipid stress in obesity, as evidenced by elevated lipid accumulation and lipolysis-related gene expression, thus contributing to the impairment in atrial Akt signaling. Taken together, our results demonstrated that melatonin could increase AF susceptibility in obesity, probably due to increased lipid stress and resultant impairment of atrial Akt signaling. Our findings suggest that special precautions should be taken when administering melatonin to obese subjects.

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.

While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.

Melatonin Nuclear Receptors Mediate Green-and-Blue-Monochromatic-Light-Combinations-Inhibited B Lymphocyte Apoptosis in the Bursa of Chickens via Reducing Oxidative Stress and Nfκb Expression.

Previous studies found that melatonin modulates a combination of green-and-blue-light-induced B-lymphocyte proliferation via its membrane receptors Mel1a and Mel1c. However, in addition to its membrane-bound receptors, melatonin also functions through binding to nuclear receptors RORα/RORβ/RORγ. In this study, we raised 120 chicks under 400–700 nm white (WW), 660 nm red (RR), 560 nm green (GG) and 480 nm blue light (BB) from P0 to P26. From P27 to P42, half of the chickens in green, blue and red were switched to blue (G→B), green (B→G) and red (R→B), respectively. We used immunohistochemistry, Western blotting, qRT-PCR, Elisa and MTT to investigate the influence of various monochromatic light combinations on the bursal B lymphocyte apoptosis and oxidative stress levels as well as estimate whether melatonin and its nuclear receptors were involved in this process. Consistent with the increase in the plasma melatonin concentration and antioxidant enzyme activity, we observed that G→B significantly decreased the RORα, RORγ mRNA level, inhibited Bax, Caspase-3 and p-iκb, p-p65 protein expression, increased the IL-10 level and Nrf2, HO-1 protein expression, down-regulated the MDA and pro-inflammatory IL-6, TNF-α and IFN-γ levels in the bursa compared with WW, RR, GG, BB and R→B, respectively. Our in vitro results showed exogenous melatonin supplementation inhibited B-lymphocyte apoptosis, decreased IL-6, TNF-α, IFN-γ and ROS production, down-regulated RORα, RORγ mRNA level and p-iκb and p-p65 protein expression, whereas it improved the IL-10 level and Nrf2 and the HO-1 protein expression in bursal B lymphocyte. Moreover, these responses were abrogated by RORα agonist SR1078 but were mimicked by RORα antagonist SR3335 or RORγ antagonist GSK2981278. In addition, p65 antagonist BAY reversed RORα/RORγ-mediated G→B-inhibited bursal B lymphocyte apoptosis. Overall, we concluded that melatonin nuclear RORα/RORγ mediates G→B-inhibited bursal B lymphocyte apoptosis via reducing oxidative stress and Nfκb expression.

How effective is daytime oral exogenous melatonin supplementation in improving sleep quality and duration?

How effective is daytime oral exogenous melatonin supplementation in improving sleep quality and duration?

Identification of SNAT Family Genes Suggests GhSNAT3D Functional Reponse to Melatonin Synthesis Under Salinity Stress in Cotton.

Serotonin N-acetyltransferase (SNAT) is a key enzyme in the biosynthesis of melatonin, and plays an important role in the regulation of melatonin synthesis. The study of SNAT is of great significance to understand the function of melatonin. In this study, we analyzed the structural characteristics, phylogenetic relationship, gene structure, expression pattern, evolutionary relationship and stress response of the members of the SNAT gene family in upland cotton through bioinformatics. A putative Serotonin n-acetyltransferase gene GhSNAT3D was identified, and preliminarily function of GhSNAT3D was verified by virus-induced gene silencing. We identified a total of 52 SNAT genes in the whole genome of G. hirsutum, and part of the GhSNATs were regulated by exogenous melatonin. The content of melatonin, antioxidant enzyme activity and Ca2+ content of GhSNAT3D gene silenced plants decreased, and the salt tolerance of GhSNAT3D gene silenced plants was reduced. Exogenous melatonin supplementation restored the salt tolerance of GhSNAT3D gene silenced plants. GhSNAT3D may interact with GhSNAT25D and ASMT to regulate melatonin synthesis. This study provided an important basis for further study on the regulation of melatonin in cotton against abiotic stress.

Sub-Chronic Exposure (90 Days) to Titanium Dioxide Nanoparticles (TiO2 NPs) Induce Alterations in Hematology and Serum Biochemistry in Male Wistar Rats: Effect of Exogenous Melatonin Supplementation

Rapid increase in the use of metal-oxide nanoparticles in many industries increased the risk of toxicity to humans. In this regard, an experimental study was conducted in male Wistar rats to study the effect of repeated-dose sub-chronic oral exposure for 90 days to titanium dioxide nanoparticles on certain hematological and serum biochemical parameters and to evaluate the ameliorative potential of melatonin to overcome such alterations. The rats were divided randomly into four groups of fourteen each. Group-I served as vehicle control, Group-II received TiO2 NPs (100mg.kg-1); Group-III received treatment similar to that of Group-II along with melatonin @10mg.kg-1, while group-IV received only melatonin. Rats exposed to TiO2 NPs showed a significant increase in WBC count at 60days and 90 days intervals, whereas a significant decrease in RBC count, platelets count, and increase in percent granulocytes only at 90 days intervals. In addition, a significant increase in the activities of serum aminotransferases, alkaline phosphatase, and gamma-glutamyl transferase was observed in rats exposed to TiO2 NPs. Melatonin supplementation significantly ameliorated some of these parameters on day 60 or 90 of the experimental period. Thus, melatonin can be a promising agent for therapeutic intervention to overcome titanium dioxide nanoparticles induce adverse effects after appropriate clinical studies.

The Effects of Melatonin on Cognition and Αβ load in an Alzheimer’s Disease Mouse Model

AbstractBackgroundThe neurohormone melatonin is released from the pineal gland and is an endogenous antioxidant and free radical scavenger that regulates sleep/wake cycle and circadian rhythm. Decline of nocturnal melatonin secretion with severe sleep disturbance has been consistently reported in Alzheimer’s Disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. However, exogenous melatonin supplementation can reduce Αβ neurotoxicity and formation while improving cognitive performance and sleep quality.MethodIn this study, the long‐term influence of melatonin on behavioral and neuropathological changes were evaluated in the 5xFAD mouse model, when treatment was started in adolescence. After ∼20 weeks of orally administered melatonin (10 mg/kg), Morris water maze behaviour was assessed in 54 mice, followed by Aβ42 quantification in hippocampal tissue.ResultOverall, transgenic mice showed impaired learning, and a significant increase in Aβ42 plaque load, replicating previous results with this strain. Melatonin marginally improved learning by decreasing distance travelled in the Morris water maze and slightly decreasing Aβ42 concentration in the hippocampus. These results support the hypothesis that long‐term melatonin supplementation may be beneficial at early stages of the disease process and should be explored more fully.ConclusionAbnormal accumulation of neurotoxic forms of Αβ occur in brain regions involved in the regulation of sleep in AD patients and the disturbed regulation of sleep that occurs early in the disease may contribute to cognitive decline by decreasing Αβ clearance. In contrast to conventional antioxidants, melatonin crosses the blood‐brain barrier, is relatively devoid of toxicity, and constitutes a straight‐forward potential therapeutic candidate in AD treatment.

Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction

Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 μg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.

263 Characterizing Vaginal Bacterial Community Composition in Brangus Heifers

Abstract The role of the reproductive tract microbiota is an emerging field receiving considerable attention in human research, whereby the vaginal microbiota has been characterized in relation to fertility, conception, pregnancy, and parturition. However, the acidic, Lactobaccillus dominated vaginal microbiota in humans contrasts the neutral, dynamic microbial environment characterized in cattle. Over the past few years, many postpartum studies in dairy cattle described a mechanism recently proposed in humans, the ascension of the vaginal microbiota into the uterine body at the onset of labor. Although bovine fetal sterility prior to parturition is under debate, the vaginal microbiota is an early contact for the neonate with microorganisms and inoculates the uterus during parturition. Thus, any changes occurring in the vaginal microbiota could have implications in dam and calf health; this, combined with ease of access, led to the current research focusing on the bovine vaginal microbiota. Characterization studies during the estrous cycle, gestation, and postpartum period have been performed, concluding the bovine vaginal microbiota is dynamic. However, due to the low abundance in the vaginal microbiota, the seemingly small taxonomic changes reported in these studies could be of great importance. Secondly, researchers have begun to evaluate the effect of exogenous and endogenous hormone concentrations on the vaginal microbiota. Little to no differences have been found except with exogenous melatonin supplementation. In pregnant heifers, exogenous melatonin altered the beta diversity of the vaginal tract by increasing aerobic bacteria present. Moreover, a study evaluating the effects of nutrient restriction on the vaginal microbiota found no taxonomic or structure differences. These findings have allowed researchers to target paucities, improve methodology, and realize the importance of the reproductive tract microbiota. In short, based on these studies, future research examining the role of the reproductive tract microbiota could uncover mechanisms vital to increasing reproductive performance.

Salivary melatonin is depleted in patients with dental caries due to the elevated oxidative stress

ObjectivesTo determine salivary melatonin and malondialdehyde levels in individuals with and without dental caries. Materials and methodsSaliva samples were collected in a fasting state from patients with active dental caries (n ​= ​16) and patients without dental caries (n ​= ​16). Melatonin was measured in the samples using a commercially available ELISA kit and malondialdehyde was assayed using a standardized spectrophotometric method. ResultsThe salivary melatonin levels were significantly lower (p ​< ​0.01) in patients with active dental caries than patients without dental caries, while the salivary malondialdehyde values were significantly higher (p ​< ​0.01) in patients with active dental caries than patients without dental caries. The binary logistic regression analysis revealed a negative correlation (−0.513) between the salivary melatonin and malondialdehyde levels which was statistically significant (p ​< ​0.042) in the patient group with active dental caries, while no such relationship could be demonstrated in the patient group without dental caries. ConclusionMelatonin depletion and augmented malondialdehyde levels potentially indicate that the endogenous melatonin has been utilized to counter the oxidative stress-induced during the initiation and progression of dental caries. Further research could explore the potential use of exogenous melatonin supplementation as a preventive and therapeutic measure for dental caries.

Melatonin: A regulator of the interplay between FoxO1, miR96, and miR215 signaling to diminish the growth, survival, and metastasis of murine adenocarcinoma.

Melatonin (Mel.), also known as the magic hormone, is a nocturnally secreted hormone orchestrates the clearance of free radicals that have been built up and cumulated during day. This study aims to detect the impact of pineal gland removal on the incidence of tumor development and to assess the signaling pathways via which exogenous melatonin counteract cancer growth. This goal has been achieved by novel approach for pineal destruction using dental micromotor which validated by melatonin downregulation in blood plasma. Mice were injected sub-cutenously with Ehrlich cells to develop solid tumor as a murine model of breast cancer. The increase at tumor markers carcino embryonic antigen, TNFα, and nuclear factor kappa-light-chain-enhancer of activated B cells was over countered by exogenous melatonin supplementation (20 mg/kg) daily for 1month. The anticancer effects of melatonin were significantly mediated by scavenging H2 O2 and NO and diminishing of lipid peroxidation marker malondialdehyde. The real-time polymerase chain Rx analyses indicated a significant effect of Melatonin in upregulating the expression of miR215, fork head box protein O1 (foxO1), and downregulation of miR96. Flowcytometric analyses indicated a significant effect of melatonin on induction of cell cycle arrest at G1 phase which was further confirmed by Ki67 downregulation. Immunohistochemical analyses indicated the role of melatonin in upregulating P53-dependent apoptosis and downregulating CD44 signaling for survivin, matrix metallo-protein kinase 2, and vascular endothelial growth factor to inhibit cell survival and metastasis. In conclusion, this study sheds the light on M./P53/miR215/CD44 with an emphasis on M./miR96//foxO1 signaling cascades, as a novel pathway of melatonin signaling in adenocarcinoma to diminish cancer cell growth, survival and metastasis.

Melatonin Enhances the Tolerance and Recovery Mechanisms in Brassica juncea (L.) Czern. Under Saline Conditions.

Melatonin has been recently known to stimulate plant growth and induce protective responses against different abiotic stresses. However, the mechanisms behind exogenous melatonin pretreatment and restoration of plant vigor from salinity stress remain poorly understood. The present study aimed to understand the effects of exogenous melatonin pretreatment on salinity-damaged green mustard (Brassica juncea L. Czern.) seedlings in terms of oxidative stress regulation and endogenous phytohormone production. Screening of several melatonin concentrations (0, 0.1, 1, 5, and 10 μM) on mustard growth showed that the 1 μM concentration revealed an ameliorative increase of plant height, leaf length, and leaf width. The second study aimed at determining how melatonin application can recover salinity-damaged plants and studying its effects on physiological and biochemical parameters. Under controlled environmental conditions, mustard seedlings were irrigated with distilled water or 150 mM of NaCl for 7 days. This was followed by 1 μM of melatonin application to determine its recovery impact on the damaged plants. Furthermore, several physiological and biochemical parameters were examined in stressed and unstressed seedlings with or without melatonin application. Our results showed that plant height, leaf length/width, and stem diameter were enhanced in 38-day-old salinity-stressed plants under melatonin treatment. Melatonin application obviously attenuated salinity-induced reduction in gas exchange parameters, relative water content, and amino acid and protein levels, as well as antioxidant enzymes, such as superoxide dismutase and catalase. H2O2 accumulation in salinity-damaged plants was reduced by melatonin treatment. A decline in abscisic acid content and an increase in salicylic acid content were observed in salinity-damaged seedlings supplemented with melatonin. Additionally, chlorophyll content decreased during the recovery period in salinity-damaged plants by melatonin treatment. This study highlighted, for the first time, the recovery impact of melatonin on salinity-damaged green mustard seedlings. It demonstrated that exogenous melatonin supplementation significantly improved the physiologic and biochemical parameters in salinity-damaged green mustard seedlings.

Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial

BackgroundThe aim of this study was to determine the efficacy of exogenous melatonin supplementation for sleep disturbances in patients with middle-aged primary insomnia. MethodsThis is a randomized double-blind, placebo-controlled parallel study. Participants were recruited from Tianlin community, Xuhui district, Shanghai. Ninety-seven consecutive middle-aged patients with primary insomnia were randomized to receive 3 mg fast-release melatonin (n = 51) or placebo (n = 46) for four-weeks. Objective sleep parameters tested by overnight polysomnography, subjective sleep performance and daytime somnolence obtained from the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were obtained at baseline and after treatment. Treatment was taken daily 1 h before bedtime. Serious adverse events and side-effects were monitored. ResultsMelatonin supplementation significantly decreased early wake time [−30.63min (95% CI, −53.92 to −7.34); P = 0.001] and percentage of N2 sleep [−7.07% (95% CI, −13.47% to −0.68%); P = 0.031]. However, melatonin had no significant effect on other objective sleep parameters including sleep latency, sleep efficiency, wake during the sleep and percent of N1, N3 and REM sleep. Melatonin had no effect on insomnia symptoms and severity on the PSQI [1.53(95% CI, −0.55 to 3.61); p = 0.504]; ISI [0.81 (95% CI, −2.27 to 3.88); p = 0.165] and ESS [−0.83 (95% CI, −3.53 to 1.88); p = 0.147]. No serious adverse events were reported. ConclusionsMelatonin supplementation over a four-week period is effective and safe in improving some aspects of objective sleep quality such as total sleep time, percentage of rapid eye movement and early morning wake time in middle-aged patients with insomnia. Trial registrationIdentifier: ChiCTR-TRC-13003997; Prospectively registered on 2 December 2013.

First evidence on protective effect of exogenous melatonin supplementation against disruption of the estrogenic pathway in bone metabolism of killifish (Aphanius fasciatus).

This study was carried out to investigate the effects of exposure to estrogen antagonist nafoxidine hydrochloride (NH) and/or melatonin (Mlt) on certain bone metabolism parameters in killifish Aphanius fasciatus, a species suggested to be a suitable model for studying spinal deformities such as scoliosis. Immature females of A. fasciatus receiving 10μg/L NH and/or 100μg/L of Mlt were used and were sacrificed 30days after the treatment. The spinal column, brain, and liver were collected and analyzed by various histological, biochemical, chemical, and molecular investigations. NH exposure increased frequency of histological alterations and caused signs of spinal column demineralization such as significant decrease in the percentage of nonorganic components content and calcium concentration. These changes were accompanied by decreased alkaline phosphatase activity (AP), hepatic insulin growth factor-1 (IGF-1) content, and, interestingly, cerebral Mlt concentration. Concomitant treatment with Mlt and NH enhanced expression of the gene encoding the Mlt receptor "mtnr1aa"and significantly restored the normal skeletal histology and the normal metabolism bone parameters. Our data suggest that disturbance of estrogen pathway in A. fasciatus induces cerebral Mlt depletion and, then, causes skeletal tissue alterations and bone demineralization and that exogenous Mlt supplementation has a protective effect. Thus, estrogen receptor antagonists and Mlt become important compounds to consider for the accurate prediction and assessment of bone physiology and spinal deformities in fish.