Effects Of Melatonin Research Articles

Effect of melatonin treatment of pregnant Sarda ewes on lactation and lamb development.

Context Melatonin administration during pregnancy can influence fetal development and lactation. Aims This study aimed to verify whether melatonin treatment of pregnant Sarda ewes in spring improved lamb weight at birth, 7 and 21days of age, time to first colostrum intake, birth behavior and survival. Additionally, we examined melatonin's effect on milk yield and composition. Methods On 18 April, 200 ewes were assigned to two groups of 100 each, based on lambing date, body condition score, parity, age and milk yield. One group received melatonin implants on 20 April, 4 July and 17 September; the other served as control. Rams (12 per group) were introduced on 25 May and removed after 40days. Lamb weight was recorded at birth, 7 and 21days, while milk yield and composition were assessed bi-weekly from day 30 of lactation. Key results Lambs born to melatonin-treated ewes were heavier at birth (3.54 vs 2.89kg), and at 7(5.21 vs 4.40kg) and 21days of age (11.3 vs 10.1kg) and reached colostrum intake sooner than lambs from untreated ewes (55.5±5.3 vs 69.4±5.6min). Milk yield was higher in melatonin-treated ewes, with somatic cell counts decreasing in treated animals and increasing in controls over the five samplings. Milk fat was higher in treated ewes than controls during early lactation, although protein and lactose levels remained similar between groups. Conclusion Melatonin treatment throughout pregnancy improved lamb growth and milk production and quality, suggesting a potential management advantage for sheep.

Lipopeptides from Bacillus atrophaeus MCM61 and melatonin suppress gray mold-induced oxidative stress in cut roses (Rosa hybrida L.) and improve vase life.

Application of melatonin and lipopeptides (LPs) derived from Bacillus strains is considered an efficient strategy to control plant diseases atboth pre and postharvest stages. However, the combined application of melatonin and LPs has not been studied yet. Therefore, the present study presents the synergistic effect of melatonin and LPs produced by Bacillus atrophaeus strain MCM61 against gray mold disease and its impact on quality parameters and vase life of cut roses. The stems of cut roses alongwith flowers were dipped in the melatonin solution at concentration (0, 0.2, 0.4, 0.6, and 0.8mM) and the results indicated thatthe vase life of flowers treated with the melatonin was enhanced compared to control. Melatonin at 0.6mM concentration showed the highest vase life of cut roses at day 8. Synergistic treatment with melatonin and LPs of B. atrophaeus MCM61 revealed that MDA and H2O2 content showed the highest decrease in cut roses. Similarly, relative water content, total phenol content, GSH content, and defense enzymes i.e., APX, SOD, PPO, POD, and CAT activities were increased in cut roses treated with co-application of B. atrophaeus MCM61 LPsand melatonin compared to single treatments and control treatment. Furthermore, the longevity of cut roses was also improved in flowers treated with a combined application of MCM61 and melatonin compared to other treatments.

Effects of Melatonin on Ginseng Leaf Phenotypic and Photosynthetic Properties Following Chilling and Freezing Stress

Spring frost damage is a significant natural disaster, which can lead to large-scale ginseng (Panax ginseng C. A. Mey) yield reduction. To determine chilling and freezing stress damage to ginseng, we designed an experiment using three-year-old potted ginseng plants. We simulated chilling (0±0.3 ℃) and freezing (-2.5±0.3 ℃, -5±0.3 ℃) in an artificial room, with 16±2 ℃ of the room temperature at night as the control, to evaluate their physiological effects on ginseng leaf spectral reflectance, photosynthetic characteristics, and chlorophyll fluorescence parameters. We also investigated the mitigating effects of exogenous melatonin on ginseng leaves exposed to chilling and freezing stress. All ginseng leaves died under -5 ℃ freezing stress and the mortality rate reached 25∼57% under -2.5 ℃ freezing stress, while no plants died under 0 ℃ chilling stress. After -2.5 ℃ and 0 ℃ stress, leaf spectral reflectance in the 750∼1000 nm band was significantly lower than the control; transpiration rate, net photosynthetic rate, intercellular CO2 concentration, and stomatal conductance decreased significantly compared with the control, and there was no significant change in recovery time. The Fv/Fm ratio and qp decreased after low-temperature stress, while NPQ increased. After one week of melatonin application, leaf spectral reflectance in the 600∼650 and 750∼1000 nm bands reflected significant differences between the effects of melatonin application and no application on ginseng leaf chlorophyll content and structure under freezing stress. Ginseng leaf net photosynthetic rate increased by 23.79% and 4.48%, while intercellular CO2 concentration increased by 33.49 and 11.83% under stress at -2.5°C and 0°C. The ginseng leaf chlorophyll fluorescence parameter (Fv/Fm) recovered to 0.8 and above in one week after melatonin application, and qp decreased under -2.5°C and 0°C stress after melatonin application. Additionally, the NPQ values were 11.44% and 4.6% lower in -2.5+MT and 0+MT, respectively, compared to the treatment without MT applied. A sudden drop in temperature to 0 ℃ or even below caused ginseng plant growth inhibition, but melatonin application at a concentration of 100 nmol L−1 had certain mitigating effects on ginseng growth, which provides a theoretical basis and technical support for ginseng production.

Exogenous melatonin improves peanut field productivity and quality at reduced nitrogen application

ContextNitrogen (N) plays integral roles in plant growth and yield. Finding ways to increase plant yield with reduced N usage will promote both agricultural and environmental sustainability. Melatonin acts as a multifunctional regulatory molecule in numerous metabolic processes crucial for plant growth and development as well as response to environmental stresses. The effects of melatonin on the material accumulation and transport, source-sink dynamics, as well as its association with yield and quality formation of peanut (Arachis hypogaea L.) remain unclear, especially at different N levels. ObjectivesWe aim to investigate the response mechanism of melatonin in peanut plants subjected to reduced N application, in order to confirm the hypothesis that melatonin regulates carbon and N accumulation and transport, and coordinates source-sink relationships to increase production and improve quality. MethodsThis study examined the effects of two seed dressing treatments (with or without 0.5μM MT) and three N fertilizer levels (90, 135, and 180kg/ha) using a randomized complete block design with split plots and three biological replications over 2021 and 2022. The evaluation focused on photosynthetic physiology, enzyme activities related to carbon and N metabolism, accumulation and transport of dry matter and N, yield, and quality, while exploring the relationships among these variables. ResultsMelatonin-treated plants had more stable carbon and N metabolism than the untreated ones. This stability was linked to improved photosynthesis, sucrose production, and N assimilation, especially at the reduced N levels (90 and 135kg/ha). Across three N levels and two years of field tests, MT increased peanut dry matter by 23.49% from 455.63g/m2 to 562.66g/m2, enhanced the accumulation and mobilization of dry matter and N to grains by increasing peanut grain mass by 22.41-29.07% at different N levels. This process appears to subsequently elevate the effective pod rate, leading to an average increase in pod yield, fat and protein content by 12.63%, 7.95%, and 10.33%, respectively, over a two-year period and across three N application levels. ConclusionsPlants subjected to melatonin treatment exhibited a coordinated source-sink relationship, which is manifested in high photosynthetic capacity and a high proportion of assimilates transported to pods, thus promoting effective proportions and pod fullness to improve peanut yield and quality under reduced N application. SignificanceOur research provided insights into the response mechanism of melatonin on peanut carbon and N metabolism across various N treatments, contributing to a deeper understanding of how melatonin enhances crop yield and quality.

MELATONIN ON SLEEP IN PARKINSON’S DISEASE: A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

BackgroundSleep disturbances are one of the most common non-motor symptoms in Idiopathic Parkinson’s Disease (IPD) patients. However, the effect of melatonin on sleep problems in Parkinson's disease patients is unclear. Aims and objectivesTo study the effect of melatonin on sleep in IPD patients through subjective and objective assessment. MethodsBetween August 2023 to February 2024, we conducted a randomized, double-blind, placebo-controlled trial on IPD patients. We randomized eligible subjects to melatonin (3mg) (n=43) or placebo (n=43) for 8 weeks. The primary endpoint was sleep quality assessed through the Pittsburgh sleep quality index and daytime sleepiness using Epworth sleepiness scale. Secondary endpoints were polysomnographic sleep parameters, quality of life, motor and non-motor symptoms. Assessments were done at baseline and at the end of 8 weeks. ResultsWe screened 107 IPD patients and 86 patients were included in the study. Seventy three patients (melatonin, 35 and placebo, 38) completed the study. The mean change in Pittsburgh Sleep Quality Index (PSQI) score between the two groups was 1.87 (95% CI: 1.5–2.1; p = 0.001) and Epworth Sleepiness Scale (ESS) score was 1.25 (95% CI: 0.80-1.71; p = 0.001) favoring melatonin. The mean difference between the two groups for Non-Motor Symptoms Scale (NMSS) was 6.11 (95% CI 5.27-6.92; p = 0.001), Parkinson's Disease Questionnaire (PDQ 39) 8.12 (95% CI 6.97-9.50; p = 0.001) & Polysomnography (PSG) parameters [sleep latency 8.36 (95% CI 4.38-12.34; p = 0.001) and total sleep time 14.51 (95% CI 5.00-24.41; p = 0.005)] favoring melatonin. Side effects attributable to melatonin were minimal. ConclusionMelatonin is an effective and safe treatment option for sleep problems in PD patients, and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life. We need to emphasize the fact that though we had statistically significant changes in our outcomes, it is not clear whether such changes would have real-life impact (meaningfulness) that would be relevant to licensing authorities or management as patients in our study are young, have short disease duration, have high use of anticholinergics and on modest levodopa equivalent dose. So, we are doubtful if this could be generalized to the typical PD population who are older, have longer disease duration and are on potentially sedating medications or not.

Melatonin nuclear receptors mediate monochromatic light-induced T-lymphocyte proliferation of thymus through the AKT/GSK3β/β-catenin pathway in chick

Based on previous research, it's unclear about the signaling pathway involved in the negative regulation of T-lymphocyte proliferation in thymus by monochromatic red light. Newly hatched chicks were randomly assigned divided into white (WL), red (RL), green (GL), and blue (BL) light treatments. Three days later, each light treatment group was further divided into intact, sham operation, and pinealectomy groups. The findings revealed that RL led to an increase in the expression of RORα and RORγ, while p-AKT/p-GSK3β/β-catenin/CyclinD1 expression in the thymus of chicks were decreased. Conversely, GL showed opposite results compared to RL. After pinealectomy, accompanied with the expression of RORα and RORγ increased under four light, p-AKT/ p-GSK3β/ β-catenin/ CyclinD1 expression were decreased. In vitro, exogenous melatonin increased the p-AKT/β-catenin/CyclinD1 expression in the thymic lymphocytes of chick reared under RL. The stimulative effect of melatonin was enhanced by SR3335 (RORα antagonist) or GSK298 (RORγ antagonist), while it was attenuated by SR1078 (RORα/RORγ agonist), LY-294 (PI3K antagonist) and HY-102 (AKT antagonist). These results demonstrate that RORα/RORγ negatively regulate monochromatic red light induced-T-lymphocyte proliferation in the thymus, possibly through the PI3K/AKT/p-GSK3β (Ser9) signaling pathway.

Melatonin induces white-to-beige adipocyte transdifferentiation through melatonin receptor 1-mediated direct browning and indirect M2 polarization.

Previous studies have shown that melatonin induces adipocyte browning in vivo. However, the underlying mechanisms of melatonin action at the cellular level remain elusive. In this study, we investigated the mechanisms underlying melatonin-induced browning in 3T3-L1 adipocytes and RAW 264.7 macrophages. Melatonin caused the transdifferentiation of fully differentiated white adipocytes into beige adipocytes, which involves the activation of melatonin receptor 1, followed by increased phosphorylation of p38 MAPK and Akt. Both luzindole (LZ), a non-selective melatonin receptor antagonist, and selective melatonin receptor 1 knockdown attenuated the browning effects of melatonin. Melatonin also induced M2 polarization in RAW 264.7, involving the melatonin receptor 1-Src-STAT3/STAT6 phosphorylation signaling cascade. Melatonin-treated M2-conditioned medium (CM) contained increased levels of catecholamine (CA) and induced beige adipocytes when treated with differentiated 3T3-L1 white adipocytes. In vivo oral administration of melatonin to high-fat diet (HFD)-induced obese (DIO) mice reduced body weight, accompanied by increased expression of uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in subcutaneous adipose tissues. Moreover, arginase-1 (Arg1) and mannose receptor C type-1 (MRC1) levels were markedly higher in the melatonin-treated groups, suggesting that melatonin induces adipose browning and M2 polarization in vivo. Collectively, melatonin-induced adipocyte browning appeared to be reflected by the sum of melatonin receptor 1-activated direct browning effects and indirect M2 polarization-mediated effects.

Melatonin protects bovine oocyte from βHB-induced oxidative stress through the Nrf2 pathway

Accumulation of ketone bodies in the blood or tissues can trigger ketosis, exerting detrimental effects on bovine oocytes maturation. Exposure to its primary component, β-hydroxybutyric acid (βHB), disrupts mitochondrial function, culminating in the excessive buildup of reactive oxygen species (ROS) and subsequent initiation of apoptosis in oocytes. These ultimately result in poor oocyte quality. Melatonin, recognized for its endogenous antioxidant properties, is capable of mitigating ROS levels and enhancing the expression of antioxidant enzymes. In this study, we explored the protective effects of melatonin on the damages induced by βHB. Melatonin was added at a concentration of 10-9 M to the culture medium on bovine oocytes. Parameters including first polar body extrusion rate, mitochondrial membrane potential, ROS, cell apoptosis were assessed. Results showed that melatonin could restore bovine oocyte maturation rate, enhance mitochondrial function, reduce cell apoptosis rate, and mitigate oxidative stress levels. Notably, Nrf2 signaling pathway inhibitor ML385 significantly attenuated the protective effects of melatonin on oxidative stress induced by βHB exposure. In summary, our study demonstrates that melatonin can protect oocytes from oxidative stress induced by βHB exposure, with indications that this protective mechanism may be mediated through the Nrf2 pathway.

Chronic Toxic Effects of Tramadol on the Brains of Adult Albino-Rats and possible Ameliorative Effects of Melatonin

Chronic Toxic Effects of Tramadol on the Brains of Adult Albino-Rats and possible Ameliorative Effects of Melatonin

Melatonin ameliorates age-related sarcopenia by inhibiting fibrogenic conversion of satellite cell

The fibrogenic conversion of satellite cells contributes to the atrophy and fibrosis of skeletal muscle, playing a significant role in the pathogenesis of age-related sarcopenia. Melatonin, a hormone secreted by the pineal gland, exhibits anti-aging and anti-fibrotic effects in various conditions. However, the effect of melatonin on satellite cell fate and age-related sarcopenia remains under-explored. Here, we report that melatonin treatment mitigated the loss of muscle mass and strength in aged mice, replenished the satellite cell pool and curtailed muscle fibrosis. When primary SCs were cultured in vitro and subjected to aging induction via d-galactose, they exhibited a diminished myogenic potential and a conversion from myogenic to fibrogenic lineage. Notably, melatonin treatment effectively restored the myogenic potential and inhibited this lineage conversion. Furthermore, melatonin attenuated the expression of the fibrogenic cytokine, transforming growth factor-β1, and reduced the phosphorylation of its downstream targets Smad2/3 both in vivo and in vitro. In summary, our findings show melatonin's capacity to counteract muscle decline and inhibit fibrogenic conversion in aging SCs and highlight its potential therapeutic value for age-related sarcopenia.Graphical

Preventive effects of melatonin and amifostine on irradiated rats with experimental periodontitis

BackgroundThe aim of this study was to investigate the preventive effects of amifostine and melatonin oxidatively, biochemically and histomorphometrically in rats with radiotherapy-induced experimental periodontitis.Methods40 female Sprague-Dawley rats were divided into 5 groups: Control, experimental periodontitis (Ep), Ep + radiotherapy (Ep + Rt), Ep + Rt + amifostine (Ep + Rt + Ami), Ep + Rt + melatonin (Ep + Rt + Mel). The day after induction of periodontitis by ligature, a single dose of 5 Gy radiotherapy was administered. On the same day, treatments with amifostine (200 mg/kg) for 3 days and melatonin (10 mg/kg) for 15 days were started. By after 23 days of experiment, periodontal bone loss was measured by histomorphometry. RANKL, OPG and Caspase-3 activities were analyzed immunohistochemically and inflammatory cytokine (IL-1β, IL-10, IL-6, TNF-α) levels and oxidative stress (TOS/TAS) were analyzed biochemically in tissue homogenates.ResultsIt was observed that there was a significant difference in many biochemical parameters and oxidative stress levels between the control group and Ep + Rt (p < 0.05). Alveolar bone destruction in the melatonin prophylaxis group was observed to be close to control (p > 0.05). Melatonin significantly improved biochemical, histochemical, apoptotic and bone loss levels in irradiated experimental periodontitis rats (p < 0.05). When comparing the two drug groups (Ep + Rt + Ami and Ep + Rt + Mel), no statistically significant difference was found at any parameter level (p > 0.05).ConclusionBoth melatonin and amifostine can significantly limit RT-induced periodontal bone loss by suppressing inflammatory stress, apoptotic mechanisms, and RANKL-related osteoclastic activity. Given the limited side effects of melatonin, it may be an alternative to amifostine.

Melatonin attenuates sepsis-induced muscle atrophy by regulating the PI3K/Akt signaling pathway

BackgroundIn intensive care units, sepsis-related muscle atrophy is a severe complication of numerous diseases, yet the underlying mechanism and potential therapeutic options remain elusive. Recent research has identified melatonin as a promising candidate for attenuating organ dysfunction triggered by sepsis. MethodsWe used in vitro and in vivo models to simulate sepsis, C2C12 myotubes were treated with LPS, and the mice underwent cecal ligation and puncture (CLP) surgery. Following a pretreatment regimen involving melatonin and the AKT inhibitor MK-2206 2HCl, we analyzed changes in p-Akt and MuRF1 protein levels, fiber cross-sectional areas, and myotube diameters. The analyses included RNA sequencing, Western blotting, qRT–PCR, and immunofluorescence staining. ResultsActivation of the PI3K/Akt pathway in skeletal muscle occurred 24 h post-CLP surgery in mice. This was accompanied by upregulated MuRF1 expression and reduced muscle fiber cross-sectional area, which culminated in muscle atrophy. However, these detrimental effects were attenuated when the mice were pretreated with melatonin via intraperitoneal injection for seven consecutive days. Similarly, LPS treatment of C2C12 myotubes activated the PI3K/Akt pathway, elevated MuRF1 expression, and markedly reduced myotube diameter after 48 h, leading to muscle atrophy. Pretreatment of C2C12 myotubes with melatonin 24 h in advance mitigated these adverse effects. However, cotreatment of C2C12 myotubes with melatonin and MK-2206 2HCl attenuated the beneficial effects of melatonin. ConclusionMelatonin can attenuate sepsis-induced muscle atrophy by regulating the PI3K/Akt pathway.

Effects of melatonin on the prevention of delirium in hospitalized older patients: systematic review and meta-analysis

ObjectivesMelatonin has been demonstrated to exert a preventive effect on delirium. This meta-analysis sought to investigate the preventive effects of melatonin and melatonin receptor agonists (ramelteon) on delirium in hospitalized elderly patients.MethodsThis systematic review and meta-analysis delineates the risk of delirium events in older hospitalized patients with melatonin/ramelteon compared with placebo, incorporating randomized controlled trials published up to 8 July 2024. The databases searched were PubMed, Embase and the Cochrane Library. The primary outcome measures were the incidence of delirium, while the secondary outcome measures were the length of hospital stay and mortality. The results are presented as odds ratios (OR) or mean differences (MD) with a 95% confidence interval. The review of publications was conducted in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Project for Systematic Review and Meta-Analysis (PRISMA). This study has been registered with INPLASY (number INPLASY202470044).ResultsA total of 2086 patients were included in 13 randomized controlled trials. The primary outcome of this meta-analysis demonstrated a statistically difference in the incidence of delirium between the melatonin and placebo groups in hospitalized elderly patients (OR = 0.59, 95% CI: 0.40–0.87, P < 0.01, I2 = 60%), particularly in those who had undergone surgery (OR = 0.60, 95%CI: 0.40–0.89, P = 0.01, I2 = 53%). No statistically differences were observed in terms of length of stay (MD=-0.07, 95%CI:-1.09-0.94, P = 0.89, I2 = 72%) and mortality (OR = 0.79, 95%CI:0.58–1.06, P = 0.12, I2 = 0%).ConclusionsMelatonin has been demonstrated to exert a protective effect on delirium in elderly patients who are hospitalized, particularly in the context of perioperative care.

Investigation of the effects of melatonin on lung tissue through the NLRP3/TLR2/NEK7 pathway in an experimental endotoxemia model.

Sepsis, a severe clinical syndrome, arises from pro-inflammatory and apoptotic processes. Its rapid progression from sepsis to severe stages necessitates timely intervention. The lipopolysaccharide (LPS) agent triggers pro-inflammatory mediator release through Toll-like receptors, particularly TLR-2, a vital biomarker in sepsis with multiple organ failure. In LPS-induced septic shock, the NEK7-mediated NLRP3 inflammasome pathway, linked to acute lung injury, is suppressed. This pathway is implicated in sepsis-induced platelet activation and septic shock development. Antioxidants like melatonin (MEL) may positively impact reducing septic shock. In microbial-induced sepsis, melatonin can regulate pro-inflammatory mediator transcriptional activation, potentially controlling the pro-inflammatory state. In the project, the histopathological impact of melatonin in lung tissue during endotoxic shock induced by the LPS agent in Sprague-Dawley rats, and its immunoreactivity to NLRP3/NEK7/TLR-2 molecules, were assessed. Lung volumes were evaluated using micro-computed tomography (Micro-CT). While bleeding, cell infiltration, and thickening of the alveolar wall were observed in the lungs of the LPS group, a reduction in these symptoms was noted in the MEL+LPS group. Expressions of NEK7, TLR2, and NLRP3 increased in both the LPS and MEL+LPS groups compared to the control group. It was determined that in the MEL+LPS group, levels of NEK7, TLR2, and Malondialdehyde (MDA) decreased compared to the LPS group. Additionally, a decrease in the total volume of lung tissue was observed in the LPS group. In this context, our study reported the therapeutic effect of melatonin on sepsis-related acute lung injury. Our study suggests that melatonin administration in the experimental endotoxemia model melatonin may help reduce lung damage by inhibiting NEK7 and TLR2 expressions.

Effect of northwestern photoperiod and exogenous melatonin on the psychoemotional state of the Syrian hamsters (Mesocricetus auratus)

Background. Among the environmental factors that influence the increase in the frequency of occurrence of psychoemotional states, great importance is attributed to the light conditions. However, the mechanisms of behaviour regulation in the mammals in non-standard light conditions and the role of melatonin in this process have not been fully studied.The aim of the study. To assess the effects of specific northern light conditions and melatonin on the behavior of Mesocricetus auratus.Methods. The animals were divided into 4 groups: LD (control), NL (northern light conditions), and LD + mel and NL + mel (melatonin, 100 μg/animal). The study of behavioral reactions, the level of emotional and phobic anxiety state of animals was carried out in the “Open field” and “Dark chamber with holes” installations.Results. Keeping M. auratus in NL had a negative effect on their behavior – a decrease in motor activity (horizontal and vertical) and the “hole-exploratory behavior”, an increase in the number of freezing and grooming reactions and the time of the first peeking out of the upper hole were revealed. It was shown that melatonin contributed to an increase in exploratory activity and a decrease in the number of anxiety acts in NL + mel group compared to NL group; the opposite effect of the hormone on these parameters was observed in LD + mel group.Conclusion. The obtained results indicate the important role of photoperiod and melatonin in regulating the behavior of seasonally breeding species.

Therapeutic effects of melatonin on the lungs of rats exposed to passive smoking

BackgroundPassive smoke has a significant impact on lung function and constitutes a critical public health issue, as smoking generates free radicals that damage the lungs and other tissues. Currently, limited research exists on whether the antioxidant melatonin can mitigate lung damage caused by smoking. This study aims to investigate the mechanisms through which melatonin alleviates acute lung disease induced by passive smoking.MethodsRats were divided into five groups (n = 6): a control group and three groups exposed to low, medium, and high concentrations of smoke, and a melatonin treatment group.ResultsData indicated that in the high concentration passive smoking group, the alveolar structure of the lung tissue was destroyed, and the total antioxidant capacity in lung tissue diminished as the concentration of smoke increased. The expressions of TNF-α, IL-6, and IL-1β exhibited similar results. The anti-apoptotic factors Bcl-2 and Bcl-xL mRNA level significantly decreased in the high concentration smoking group, while no significant changes were observed in the medium and low concentration groups. Conversely, the high concentration passive smoking increased the pro-apoptotic factors Bax and Caspase-3 mRNA levels. Additionally, endogenous melatonin levels in lung tissue gradually decreased following exposure to smoke, whereas the exogenous melatonin alleviated the changes in inflammatory factors and apoptosis-related factors in lung tissue. Furthermore, at high smoking concentrations, the mRNA levels of lung cancer-related genes vascular endothelial growth factor (VEGF), cytochromeP450 1A1 (CYP1A1), and cytochrome P450 1B1 (CYP1B1) were significantly increased, while exogenous melatonin reduced the expression of these genes in lung tissue.ConclusionsThese findings suggest that melatonin can diminish lung tissue damage, apoptosis, and inflammatory responses induced by passive smoking, as well as decrease the expression of lung cancer-related genes. Further experimental investigations involving exogenous melatonin treatments will be needed.

Melatonin Ameliorates Cadmium‐Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism

ABSTRACTCadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd‐induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd‐induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry‐based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd‐induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine‐specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd‐exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut‐derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro‐β‐muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd‐exposed mice. However, MT could not ameliorate Cd‐induced liver damage and fibrosis in Abx‐treated mice. Conversely, MT still exerted a protective effect on Cd‐induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd‐exposed intestinal epithelial cell‐specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd‐induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR‐mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.

Therapeutic potential of melatonin-pretreated human dental pulp stem cells (hDPSCs) in an animal model of spinal cord injury

Dental pulp stem cells (DPSCs) show potential for treating neurodegenerative and traumatic diseases due to their neural crest origin. Melatonin (MT), an endogenous neurohormone with well-documented anti-inflammatory and antioxidant properties, has shown promising results with MSCs in terms of engraftment, proliferation, and neuronal differentiation in animal SCI models. However, the effects of melatonin preconditioning on human dental pulp stem cells (hDPSCs) for SCI treatment remain unclear. This study investigates the impact of melatonin preconditioning on hDPSCs engraftment, neural differentiation, and neurological function in rats with SCI. Forty-two male Sprague–Dawley rats were divided into six groups: Control, Sham, Model, Vehicle, Lesion Treatment A (SCI + hDPSCs), and Lesion Treatment B (SCI + MT-hDPSCs). After obtaining hDPSCs, stem cells were evaluated using flow cytometry. Cell viability was assessed using the MTT assay. SCI was induced in the Model, Vehicle, Lesion Treatment A, and Lesion Treatment B groups. The Lesion Treatment A and B groups received hDPSCs and hDPSCs pretreated with melatonin, respectively, 1 week after SCI, while the Vehicle group received only an intravenous injection of DMEM to simulate treatment. The other groups were used for behavioral testing. Immunohistochemistry (IHC) was employed to assess hDPSCs engraftment and differentiation at the SCI site. Motor function across the six groups was evaluated using the Basso, Beattie, and Bresnahan (BBB) score. Histological studies and cell counts confirmed hDPSCs implantation at the injury site, with a significantly higher presence in the MT-hDPSCs compared to hDPSCs (p < 0.01). IHC revealed that hDPSCs and MT-hDPSCs differentiated into neurons and astrocytes, with greater differentiation observed in the MT-hDPSCs compared to the hDPSCs (p < 0.01 and p < 0.05, respectively). Functional improvement was noted in both SCI + hDPSCs and SCI + MT-hDPSCs groups compared to SCI and Vehicle groups from Week 4 onward (p < 0.001). Significant differences were also observed between the SCI + hDPSCs and SCI + MT-hDPSCs groups starting from Week 7 (p < 0.01). Preconditioning hDPSCs with melatonin enhances engraftment, neuronal differentiation, and greater performance improvement compared to hDPSCs alone in the SCI animal model.

Effects of Melatonin Pre- and Post-Drought Treatment on Oxidative Stress Markers and Expression of Proline-Related Transcripts in Young Wheat Plants.

Wheat can tolerate a mild water deficit, but prolonged drought causes a number of detrimental physiological changes resulting in a substantial decrease in productivity. The present study evaluates the potential of the natural plant growth regulator melatonin to alleviate the negative effects of moderate drought in two Bulgarian winter wheat cultivars at the early vegetative stage. Melatonin doses of 75 µM were root-supplemented 24 h before or after the stress period. The levels of several biometric parameters, osmolyte content and stress indicators as well as the expression of genes coding for key enzymes of the proline biosynthesis pathway were analyzed in leaves at the end of the drought stress and after two and four days of recovery. Applied alone, melatonin did not exert significant effects on most of the monitored parameters. Water deprivation negatively affected seedlings' fresh weight and water content and increased the stress markers and osmolyte levels. These were accompanied by a high accumulation of TaP5CS and TaP5CR transcripts coding for the enzymes Δ-pyrroline-5-carboxylate synthase and Δ-pyrroline-5-carboxylate reductase, respectively. The effect of melatonin in reducing drought stress was similar whether applied before or after exposure, though slightly more effective when used as a pre-treatment.

Estimation of the adaptogenic potential of melatonin on salinity resistance of spring wheat seeds and sprouts

The current paper is devoted to the study of melatonin as an adaptogen capable of increasing wheat tolerance to stress caused by excess levels of easily soluble salts in the environment. The purpose of the study was to evaluate, within the framework of a laboratory model experiment, the ability of melatonin to increase seed germination and stimulate growth processes in wheat sprouts against the background of salinity. The study was conduc ted at the FSBI All-Russian Scientific Research Institute of Agrochemistry named after D.N. Pryanishnikov in 2024. The study objects were seeds of the spring wheat variety ‘Darya’. Before the experiment, the seeds were treated with aqueous solutions of melatonin in concentrations of 0; 0.01; 0.1; 1 and 10 mg/l using the priming method. Distilled water and a 150 mM sodium chloride solution were used as background solutions for germination. As a result, there has been shown that within the framework of the experiment, there is an increase in seed germination against the background of treatment with melatonin solutions in concentrations from 0.1 to 10 mg/l against a saline background. Seed treatment with melatonin has demonstrated a pronounced growth-stimulating effect on wheat sprouts, especially in relation to the root system. However, the strength of this effect was somewhat reduced on a saline background compared to control conditions. There was a maximum growth-stimulating effect of melatonin on both backgrounds when using a solution with a concentration of 1 mg/l. There was also established that priming seeds with melatonin promoted water retention in seedling root cells, which may be one of the mechanisms for increasing plant resistance to salinity.