Melatonin Levels Research Articles

Melatonin in Human Milk: A Scoping Review.

Melatonin is vital in human circadian rhythm and infant development. This scoping review summarized the current knowledge about melatonin's presence and effects in human milk to promote better understanding of its secretion pattern and clinical advancement of maternal-infant health. The review followed the Joanna Briggs Institute guideline and answered the question: What is the current knowledge about melatonin hormone in human milk? The databases searched were PubMed, CINAHL, SCOPUS, Web of Science, LILACS, Scielo, EMBASE, Science Direct, Eric, Cochrane, in addition to grey literature and reference lists of included sources. Research papers included English, Spanish, or Portuguese languages, regardless of study type or publication date. The study selection and data extraction involved two independent reviewers. Twenty-nine studies met inclusion criteria. The studies, conducted between 1993 and 2023, employed diverse designs, with cross-sectional studies being the most prevalent. Melatonin concentration exhibited a consistent pattern, being higher at night, and elevated in colostrum. The analysis methods for melatonin concentration evolved, with recent advancements contributing to more accurate measurements. Factors influencing melatonin levels, such as delivery type, maternal age, and health conditions, demonstrated a complex relationship, potentially impacting the health and development of infants. The dynamic nature of melatonin in human milk calls for continued interdisciplinary research, bridging gaps between clinical, biochemical, and epidemiological perspectives. Standardizing melatonin analysis methods are needed. Nurses should assess factors influencing melatonin levels in milk to promote interventions and guidance aimed at enhancing the regulation of the circadian cycle during the perinatal period and its benefits.

Phytomelatonin: From Intracellular Signaling to Global Horticulture Market.

Melatonin (N-acetyl-5-methoxytryptamine), a well-known mammalian hormone, has been having a great relevance in the Plant World in recent years. Many of its physiological actions in plants are leading to possible features of agronomic interest, especially those related to improvements in tolerance to stressors and in the postharvest life of fruits and vegetables. Thus, through the exogenous application of melatonin or by modifying the endogenous biosynthesis of phytomelatonin, some change can be made in the functional levels of melatonin in tissues and their responses. Also, acting in the respective phytomelatonin biosynthesis enzymes, regulating the expression of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acetyltransferase (SNAT), N-acetylserotonin O-methyltransferase (ASMT), and caffeic acid O-methyltransferase (COMT), and recently the possible action of deacetylases on some intermediates offers promising opportunities for improving fruits and vegetables in postharvest and its marketability. Other regulators/effectors such as different transcription factors, protein kinases, phosphatases, miRNAs, protein-protein interactions, and some gasotransmitters such as nitric oxide or hydrogen sulfide were also considered in an exhaustive vision. Other interesting aspects such as the role of phytomelatonin in autophagic responses, the posttranslational reprogramming by protein-phosphorylation, ubiquitylation, SUMOylation, PARylation, persulfidation, and nitrosylation described in the phytomelatonin-mediated responses were also discussed, including the relationship of phytomelatonin and several plant hormones, for chilling injury and fungal decay alleviating. The current data about the phytomelatonin receptor in plants (CAND2/PMTR1), the effect of UV-B light and cold storage on the postharvest damage are presented and discussed. All this on the focus of a possible new action in the preservation of the quality of fruits and vegetables.

Gut microbiota-melatonin signaling axis in acute pancreatitis: Revealing the impact of gut health on pancreatic inflammation and disease severity in a case-control study.

Acute pancreatitis (AP), a severe inflammatory condition affecting the pancreas requires investigation into its predictors. Melatonin, a compound with anti-inflammatory and antioxidant properties, has shown promise in managing AP. Additionally, the gut microbiota, a community of microorganisms residing in the intestines has been linked to AP development. This study aims to explore the correlation between melatonin and gut microbiota in predicting AP severity. This study involved 199 participants, with 99 diagnosed with AP and 100 serving as healthy controls. The AP patients were categorized into 2 groups based on the severity of their condition: mild AP (MAP) and severe AP (SAP). Serum melatonin levels were measured on Days 1, 3, and 5 of hospitalization, and gut microbiota composition was examined via 16S rRNA gene sequencing. Other parameters were evaluated, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, Ranson, and Acute Gastrointestinal Injury (AGI) scores. Melatonin levels were significantly lower in subjects with severe AP compared those with mild AP (18.2 ng/mL vs 32.2 ng/mL, P = .001), and melatonin levels decreased significantly in patients with AP on Days 3 and 5. The study also revealed that individuals with AP exhibited a significantly altered gut microbiota composition compared to control individuals, with a lower Shannon index and higher Simpson index. The AUCs for Simpson index and F/B ratio were significantly higher than those for other biomarkers, indicating that these gut microbiota markers may also be useful for AP prediction. The study proposes that there is a relationship between melatonin levels and the dynamics of gut microbiota profiles in relation to the severity of AP. As a result, the severity of the disease can be assessed by assessing the levels of serum melatonin and gut microbiota profiles.

Exogenous melatonin delays yellowing in postharvest broccoli by regulation of ABA and carotenoid metabolite

Yellowing is the first visible sign of floret senescence and quality deterioration in broccoli, mainly caused by chlorophyll degradation and carotenoid accumulation. In this study, the impacts of melatonin (MLT) treatment on anabolism, catabolism and storage of carotenoid in postharvest broccoli associated with ABA regulation were investigated at transcript and metabolic levels. Results showed that MLT treatment effectively repressed yellowing and senescence along with a decrease in respiration rate and ethylene emission, enhancing endogenous MLT and abscisic acid (ABA) levels. A total of 925 metabolites were differentially expressed between the control and MLT treatment, which were mainly classified into amino acids, sugars, lipids, flavonoids and others. Specific analysis revealed that MLT treatment decreased sugars, lipids, flavonoids, and aromatic amino acids, but increased aliphatic amino acids. Meanwhile, MLT treatment suppressed the expression levels of genes related to carotenoid anabolism (BoPSY, BoPDS, BoZDS, BoCRTISO, BoLCYB, BoVDE, and BoZEP) and storage (BoOR), but the genes involved in carotenoid catabolism (BoNCED2, BoNCED6, BoCCD1 and BoCCD7) were up-regulated, which could collectively result in a decrease in the levels of β-carotene and lutein and an increase in ABA level. Moreover, correlation analysis indicated that lutein content was positively correlated with BoVDE, BoPDS and BoZDS, and negatively correlated with ABA level. Thus, MLT treatment slowed down the yellowing of broccoli during storage, which might be ascribed to inhibiting the anabolism and storage of carotenoid and promoting carotenoid catabolism and ABA biosynthesis.

SlTDC modulates photosynthesis of senescent leaves in tomato

Melatonin (MT) is a key regulator in plants’ response to leaf senescence induced by aging or various abiotic stresses. Here, we demonstrated that darkness and leaf aging enhance endogenous MT levels by upregulating key genes involved in MT synthesis. Additionally, exogenous MT application significantly mitigated leaf senescence induced by darkness and leaf aging in tomato plants, leading to higher chlorophyll content and maximum photochemical efficiency (Fv/Fm) compared to the control. Using Solanum lycopersicum L. tryptophan decarboxylase (SlTDC)-overexpressed and -knockout transgenic tomato seedlings, we found that SlTDC overexpression increased endogenous MT content and suppressed mRNA levels of chlorophyll degradation-related genes: pheophorbide a oxygenase (PAO), pheophytinase (PPH), and non-yellow coloring1 like (NOL). Furthermore, SlTDC overexpression alleviated photosystem II complex (PSII) photoinhibition, increased ribulose-1,5-bisphosphate carboxylase (Rubisco) and Rubisco activase (RCA) activities and mRNA levels, and maintained higher photosynthetic efficiency in leaves under darkness and in leaves aged over 35 d compared to wild-type plants. Conversely, SlTDC knockout accelerated darkness- or leaf aging-induced leaf senescence in tomatoes. Our findings suggest that MT application or SlTDC overexpression can effectively alleviate leaf senescence by regulating photosynthesis in tomato plants.

Melatonin hormone level in nurses and factors affecting it; Investigation according to shift working pattern

This study aimed to determine the relationship between melatonin hormone levels, sleep, and factors affecting sleep, psychological resilience, and depression in nurses working with a shift work system. Conducted between February 5–12, 2021, at the Training and Research Hospital in Ağrı province, the descriptive study included 41 night shift nurses and 35 day shift nurses, totaling 76 participants. Blood samples for melatonin analysis were collected and data were gathered using the Sociodemographic Information Form, Epworth Sleepiness Scale, Sleep Disorder Scale Short Form, Brief Psychological Resilience Scale, and Beck Depression Scale Short Form. Melatonin analysis was performed using the ELISA method. Statistical significance was set at p < 0.05. Results showed that sleep disorders were present in all nurses with <7 h of daily sleep. Factors such as the use of sleeping pills, marital status, age, and gender affected sleep disorders. Mean scores for melatonin levels were 67.82 ± 40.20 for night shift nurses and 68.08 ± 39.62 for day shift nurses, with no significant difference between shifts. Similarly, no significant differences were found in daytime sleepiness (7.49 ± 4.47 vs. 7.51 ± 4.65), sleep disturbance (24.71 ± 7.33 vs. 25.23 ± 6.64), psychological resilience (18.42 ± 4.19 vs. 17.89 ± 4.74), or depression (3.22 ± 2.60 vs. 3.49 ± 3.35). Nurses exhibited mild sleep disturbances, low depression tendencies, and moderate psychological resilience. Increased daytime sleepiness and sleep disorders correlated with higher depression tendencies and lower psychological resilience. Hospital management and education units are recommended to conduct interventions on sleep quality, depression, and psychological resilience to raise awareness among nurses.

Mitochondria of Porcine Oocytes Synthesize Melatonin, Which Improves Their In Vitro Maturation and Embryonic Development.

The in vitro maturation efficiency of porcine oocytes is relatively low, and this limits the production of in vitro porcine embryos. Since melatonin is involved in mammalian reproductive physiology, in this study, we have explored whether endogenously produced melatonin can help in porcine oocyte in vitro maturation. We have found, for the first time in the literature, that mitochondria are the major sites for melatonin biosynthesis in porcine oocytes. This mitochondrially originated melatonin reduces ROS production and increases the activity of the mitochondrial respiratory electron transport chain, mitochondrial biogenesis, mitochondrial membrane potential, and ATP production. Therefore, melatonin improves the quality of oocytes and their in vitro maturation. In contrast, the reduced melatonin level caused by siRNA to knockdown AANAT (siAANAT) is associated with the abnormal distribution of mitochondria, decreasing the ATP level of porcine oocytes and inhibiting their in vitro maturation. These abnormalities can be rescued by melatonin supplementation. In addition, we found that siAANAT switches the mitochondrial oxidative phosphorylation to glycolysis, a Warburg effect. This metabolic alteration can also be corrected by melatonin supplementation. All these activities of melatonin appear to be mediated by its membrane receptors since the non-selective melatonin receptor antagonist Luzindole can blunt the effects of melatonin. Taken together, the mitochondria of porcine oocytes can synthesize melatonin and improve the quality of oocyte maturation. These results provide an insight from a novel aspect to study oocyte maturation under in vitro conditions.

The Role of Melatonin and Matrix Metalloproteinases in Breast Cancer Pathogenesis: A Comprehensive Review

Background: Breast cancer is a heterogeneous disease with molecular subtypes including Triple Negative Breast Cancer (TNBC), HER2/neu-positive, Luminal Type A, and Luminal Type B, each with unique clinical behaviors and therapeutic responses. This study investigates the role of melatonin, matrix metalloproteinases (MMPs), pro-inflammatory cytokines (IL6 and TNF-alpha), and lactate dehydrogenase (LDH) isoenzymes in breast cancer pathogenesis. Methods: Over three years, 171 breast cancer patients were studied. Blood and urine samples were collected to measure melatonin, MMPs, IL-6, TNF-alpha, LDH-1, and LDH-5 levels. Circulating tumor cells (CTCs) were isolated using density gradient centrifugation and immunomagnetic separation. Melatonin receptor expression on CTCs was analyzed by flow cytometry and immunocytochemistry. Plasma concentrations of melatonin were measured using high-performance liquid chromatography (HPLC), and MMPs, IL-6, TNF-alpha, LDH isoenzymes were quantified using enzyme-linked immunosorbent assays (ELISAs) and electrophoretic methods. Results: The expression of melatonin receptors was lowest in TNBC patients, higher in HER2/neu-positive and ER/PRnegative patients, and highest in Luminal Type A and B patients. TNBC patients exhibited elevated LDH-1 and inflammatory cytokines (IL-6, TNF-alpha), with significantly decreased melatonin levels. HER2/neu-positive patients showed elevated LDH5 and moderate decreases in melatonin. Luminal Type B and A patients had varying degrees of biomarker elevation and melatonin receptor expression. Discussion: The findings suggest a correlation between reduced melatonin signaling and aggressive breast cancer phenotypes, particularly TNBC. Elevated MMPs and pro-inflammatory cytokines underscore the role of inflammation and ECM degradation in cancer progression. Melatonin’s potential inhibitory effects on these pathways highlight its therapeutic promise. The combined assessment of melatonin, MMPs, cytokines, and LDH could guide personalized treatment strategies. Conclusion: This study underscores melatonin’s multifaceted role in breast cancer pathogenesis. Melatonin receptor expression, along with MMP, IL-6, TNF-alpha, and LDH levels, provides a detailed molecular landscape of breast cancer subtypes. Integrating melatonin supplementation into therapeutic regimens holds promise for improving outcomes, particularly inaggressive subtypes like TNBC. Further research and clinical trials are essential to validate these findings and develop effective melatonin-based therapies.

P-708 melatonin alleviates circadian rhythm disruption-induced enhanced luteinizing hormone pulsatility and ovarian dysfunction in vivo and in vitro

Abstract Study question Is melatonin deficiency a reversible cause of abnormal pattern of luteinizing hormone (LH) pulsatility and ovarian dysfunction caused by circadian rhythm disruption (CRD)? Summary answer Melatonin could rescue the augmented LH pulsatility and reproductive abnormalities caused by CRD. What is known already Melatonin, mainly synthesized and released by pineal gland, engages in regulating circadian rhythms. When circadian rhythms are disrupted, the nocturnal productions of melatonin are suppressed. Evidence suggests that circadian rhythm disruption (CRD) is associated with reproductive dysfunctions, while melatonin plays a vital role for female reproduction as a free radical scavenger and a neuroendocrine regulator. The gonadotrophin-releasing hormone (GnRH) drives pulsatile luteinizing hormone (LH) secretion, which is also essential for fertility. Study design, size, duration We used 90 CBA/CaJ mice to establish the chronic jet-lag model in which mice were exposed to an 8 hr time shift every 3 days. After 8 weeks of jet-lag induction, some of the mice were given melatonin treatment for 4 weeks. Furthermore, we used a perfusion system in vitro to mimic the process of CRD-induce high-frequency GnRH pulses stimulation of LβT2 gonadotrope cells. Participants/materials, setting, methods Repetitive tail-tip blood collection was used to evaluate the pattern of LH pulsatility. Blood plasma samples were collected from 4 mice at 4-hour intervals to measure levels of melatonin. Follicular development was evaluated by ovarian histology. Reproductive hormones was detected by ELISA. Immunohistochemistry and western blot were used to detect the expression of melatonin receptor 1A (MT1). The LβT2 cells were exposed to pulsatile GnRH at high pulse frequencies to mimic augmented pulsatile GnRH stimulation. Main results and the role of chance CRD mice exhibited reproductive-endocrine dysfunction, including irregular estrous cycles, reduced number of corpus lutea (CL), and decreased levels of estradiol and progesterone. Additionally, CRD enhanced the frequency and amplitude of LH pulsatility and pituitary LH beta-subunit expression. Melatonin administration alleviated these CRD-induced reproductive abnormalities and reversed the augmented LH pulsatility. The expression of MT1 decreased in the anterior pituitaries of CRD mice but increased after melatonin treatment, indicating the essential role of MT1 in melatonin’s reversal of CRD-induced enhanced LH pulsatility. Limitations, reasons for caution Further research is needed to validate the applicability and safety of these findings in humans. Wider implications of the findings The results suggest that melatonin may be a beneficial option for patients with reproductive-endocrine abnormalities, particularly those with circadian rhythm disruption. Trial registration number 82101719

КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ СУТОЧНОГО МОНИТОРИРОВАНИЯ АРТЕРИАЛЬНОГО ДАВЛЕНИЯ И ЦИРКАДНОГО СИНТЕЗА МЕЛАТОНИНА В ПРОГНОЗИРОВАНИИ СИНДРОМА ОБСТРУКТИВНОГО АПНОЭ СНА У ПАЦИЕНТОВ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ I-II СТЕПЕНИ

Objective. To study the role of 24-hour ambulatory blood pressure monitoring (ABPM) and circadian melatonin (MT) synthesis in predicting obstructive sleep apnea syndrome (OSAS) in patients with grade 1-2 arterial hypertension (AH) and to reveal the relationship between the study findings. Material and methods. 67 patients aged 50.0 (41.0; 56.0) having grade 1-2 AH were examined and divided into 2 groups in regard to the complex of clinical and instrumental research methods: Group 1 – 25 patients having AH and Group – 45 patients having AH associated with OSAS. 24-hour ABPM, anthropometric measurements, and respiratory monitoring were performed. MT levels were evaluated by the content of its metabolite 6-sulfatoxymelatonin (6-COMT) in the urine. Results It has been found that according to ABPM diastolic blood pressure variability during the day was ≥12 mm Hg and had high sensitivity (74.1%) and specificity (91.7%) for predicting the OSAS in patients with hypertension receiving standard antihypertensive therapy. The characteristic feature of the daily MT production in patients with AH in combination with OSAS is an increase in the level of 6-SOMT in daily urine (p=0.031) and its daily portion (p=0.037), correlating with the severity of OSAS (r=0.43; p=0.00065 and r=0.40; p=0.00079, respectively) and independent of the grade of AH (p&gt;0.05). Conclusion. The obtained results allow us to recommend the use of ABPM as a screening, low-cost study to predict OSAS in patients with grade 1-2 AH. The identified changes in the daily rhythm of MT synthesis weakly correlate with the severity of OSAS and the degree of hypertension.

Exogenous melatonin delays yellowing in harvested broccoli by maintaining chloroplast integrity

Yellowing of broccoli is a crucial limiting factor for its commercial value and consumer acceptance during postharvest. In this study, the impacts of exogenous melatonin (MEL) on chlorophyll content and fluorescence, as well as ultrastructure and membrane lipid metabolism of chloroplasts in broccoli were investigated during postharvest. The results showed that MEL treatment (200 μmol L−1) maintained the chlorophyll content, chloroplast autofluorescence and integral structure, and reduced the level ofserotonin in the chloroplasts in broccoli. Also, MEL treatment inhibited the membrane lipid peroxidation of chloroplasts, as indicated by low levels of superoxide anion (O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA), and high levels of endogenous MEL. In addition, the stability and fluidity of chloroplast membranes were also better maintained in the treated broccoli via increasing the contents of phosphatidylglyceroland (PG), monogalactosyldiglyceride (MGDG), digalactosyldiglyceride (DGDG) and unsaturated fatty acids as well as decreasing saturated fatty acid content and the activities of lipoxygenase (LOX) and lipase (LPS). Thus, the application of MEL facilitated the maintenance of chloroplast integrity, thus contributing to yellowing postponement and the extension of the storage life of broccoli.

Assessing the Effect of Exogenous Melatonin on Orthodontic Tooth Movement.

To examine the effect of orthodontic tooth movement on experimental Wistar rats by synthesizing melatonin formulation for administration and conducting serological analysis of alkaline phosphatase (ALP) and melatonin, along with histological evaluation and immunohistochemistry analysis of ALP and interleukin-6 (IL-6) in both control and experimental groups. Nine male Wistar rats were randomly divided into negative (n = 3), positive control (n = 3), and experimental groups (n = 3). Endogenous melatonin levels (pg/mL) were assessed, and an orthodontic force of 10 cN was applied to positive control and experimental groups using a ligature wire. The experimental group received a daily dose of 10 mg/kg melatonin via intraperitoneal injection. After eight weeks, blood samples and radiographs were collected, and mandible sections were prepared for histopathological and immunohistochemical evaluation. The radiographic evaluation shows minimal orthodontically induced tooth movement in comparison to the positive control group. In serological analysis, ALP was found to be increased in rats under the melatonin group. And, in the immunohistochemical evaluation, ALP was found to be increased in the melatonin group, whereas IL-6 was found to be decreased in the same (P= 0.027). The study elucidates that the administration of exogenous melatonin during orthodontic tooth movement in Wistar rats induces bone formation and inhibits resorption, eventually decelerating the process of orthodontic tooth movement. Our study emphasizes melatonin's dualistic role in stimulating bone production and suppressing resorption, offering potential therapeutic clinical implications in orthodontics.

Probiotics administration alleviates cognitive impairment and circadian rhythm disturbance induced by sleep deprivation

Gut microbiome is indispensable for maintaining normal brain function. Specifically, gut microbiota plays a causal role in sleep deprivation (SD)-induced cognitive impairment. In this study, neurobehavioral effects of the Bifidobacterium breve strain (CCFM1025) were assessed in sleep-deprived mice. CCFM1025 improved the body weight and food and water intake of the mice. It also alleviated SD-induced cognitive behavioural abnormalities (in the novel object recognition test), but did not show beneficial effects on mood- and spatial memory-related behaviours. CCFM1025 significantly altered the gut microbial composition and genome function. Key microbial metabolites that may regulate sleep function were also identified, such as isovaleric acid and γ-aminobutyric acid in the gut and purine metabolites in the serum. Those metabolites may participate in gut-brain communication by acting on the striatal melatonin system, for example to increase melatonin levels, and by regulating the expression of circadian clock genes such as those encoding the adenosine A2A receptor and period circadian regulator 1. Collectively, administration of probiotics alleviated cognitive impairment and circadian rhythm disturbance induced by SD via modulation of gut microbiome and its metabolites. These findings may help guide the treatment of insomnia or other sleep disorders via dietary strategies.

Low plasma melatonin levels negatively correlate with melasma severity

Background: Chronic exposure to ultraviolet light plays a role in the pathogenesis of melasma. Exposure to excessive sunlight leads to the formation of free radicals. As a result, the body responds by forming antioxidants such as melatonin, which is activated through the melatoninergic antioxidative system to fight oxidative stress. The relationship between melatonin and melasma is yet to be elucidated. This study aims to determine the correlation between melatonin and the severity of melasma. Methods: This analytical cross-sectional study involved 50 melasma subjects and 10 non-melasma subjects who met the inclusion criteria and were aged between 21-50 years at Prof. I.G.N.G. Ngoerah National General Hospital, Denpasar. The severity of melasma was measured by calculating the melasma area severity index (MASI) score and plasma melatonin levels were assessed using the ELISA method. Results: The median plasma melatonin level in the melasma subjects was lower (92.48 ng/ml) than in non-melasma subjects (436.35 ng/ml), with a p-value of Conclusion: Low plasma melatonin levels negatively-correlate with the severity of melasma.

Exploring the Therapeutic Potential of Benzoxazolone Derivatives on the Circadian Clock: An In Silico and Hypothetical Approach

Objective: Pain conditions exhibit variations linked to circadian rhythms. Circadian rhythms, regulated by clock proteins, impact melatonin levels and immune functions. Melatonin, structurally similar to indomethacin, a non-steroidal anti-inflammatory drug, serves as an alternative in pain-related conditions. Literature suggests a correlation between melatonin-dependent regulation of circadian rhythm and reductions in pain complaints. 2(3&lt;i&gt;H&lt;/i&gt;)-Benzoxazolone, known for its anti-inflammatory and analgesic properties, is a promising scaffold for drug design. In this study, pharmacophore analysis focused on benzoxazolone derivatives, evaluating their impact on clock proteins, and providing insights into potential chronotherapeutic implications. Methods: Molecular docking and dynamics simulations were conducted on CLOCK:BMAL1, PER1, PER2, CRY1, and CRY2 clock proteins using benzoxazolone and its 5-substituted derivatives. Molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations were employed to analyze binding free energies. Benzoxazolone derivatives, especially 5-nitro-2-benzoxazolone and 5-fluoro-2-benzoxazolone, exhibited elevated binding affinities on clock proteins compared to melatonin and indomethacin, the reference molecules. The interaction profiles and stability of complexes were maintained throughout the simulations. Results: The results suggest a regulatory impact on CRY proteins, emphasizing their role in circadian rhythm and pain modulation. In addition, the benzoxazolone ring and its derivatives, structurally resembling the core structure of melatonin and indomethacin, demonstrate promising affinities on clock proteins. Conclusion: These findings provide preliminary data and hypothetically propose benzoxazolone derivatives as potential candidates for dual functionality in analgesic activity and circadian rhythm regulation, warranting further in vitro and clinical investigations.

Melatonin-Induced Chromium Tolerance Requires Hydrogen Sulfide Signaling in Maize.

Both melatonin and hydrogen sulfide (H2S) mitigate chromium (Cr) toxicity in plants, but the specific interaction between melatonin and H2S in Cr detoxification remains unclear. In this study, the interaction between melatonin and H2S in Cr detoxification was elucidated by measuring cell wall polysaccharide metabolism and antioxidant enzyme activity in maize. The findings revealed that exposure to Cr stress (100 μM K2Cr2O7) resulted in the upregulation of L-/D-cysteine desulfhydrase (LCD/DCD) gene expression, leading to a 77.8% and 27.3% increase in endogenous H2S levels in maize leaves and roots, respectively. Similarly, the endogenous melatonin system is activated in response to Cr stress. We found that melatonin had a significant impact on the relative expression of LCD/DCD, leading to a 103.3% and 116.7% increase in endogenous H2S levels in maize leaves and roots, respectively. In contrast, NaHS had minimal effects on the relative mRNA expression of serotonin-Nacetyltransferase (SNAT) and endogenous melatonin levels. The production of H2S induced by melatonin is accompanied by an increase in Cr tolerance, as evidenced by elevated gene expression, elevated cell wall polysaccharide content, increased pectin methylesterase activity, and improved antioxidant enzyme activity. The scavenging of H2S decreases the melatonin-induced Cr tolerance, while the inhibitor of melatonin synthesis, p-chlorophenylalanine (p-CPA), has minimal impact on H2S-induced Cr tolerance. In conclusion, our findings suggest that H2S serves as a downstream signaling molecule involved in melatonin-induced Cr tolerance in maize.

Melatonin differentially refines the metabolome to improve seed formation during grain developmental stages and enhances yield in two contrasting rice cultivars, grown in arsenic-contaminated soil

The manuscript revealed the ameliorative effects of exogenous melatonin in two distinct reproductive stages, i.e., developing grains (20 days after pollination) and matured grains (40 days after pollination) in two contrasting indica rice genotypes, viz., Khitish (arsenic-susceptible) and Muktashri (arsenic-tolerant), irrigated with arsenic-contaminated water throughout their life-cycle. Melatonin administration improved yield-related parameters like rachis length, primary and secondary branch length, number of grains per panicle, number of filled and empty grains per panicle, grain length and breadth and 1000-grain per weight. Expression of GW2, which negatively regulates grain development, was suppressed, along with concomitant induction of positive regulators like GIF1, DEP1 and SPL14 in both Khitish and Muktashri. Melatonin lowered arsenic bioaccumulation in grains and tissue biomass, more effectively in Khitish. Unregulated production of reactive oxygen species, leading to cellular necrosis caused by arsenic, was reversed in presence of melatonin. Endogenous melatonin level was stimulated due to up-regulation of the key biosynthetic genes, SNAT and ASMT. Melatonin enhanced the production of diverse antioxidants like anthocyanins, flavonoids, total phenolics and ascorbic acid and also heightened the production of thiol-metabolites (cysteine, reduced glutathione, non-protein thiols and phytochelatin), ensuring effective chelation and arsenic detoxification. Altogether, our observation, supported by principal component analysis, proved that melatonin re-programs the antioxidative metabolome to enhance plant resilience against arsenic stress to mitigate oxidative damages and reduce arsenic translocation from the soil to tissue biomass and edible grains.

UP165, standardized corn leaf extract and its active component 6-methoxybenzoxazolinone induce non-rapid eye movement sleep through melatonergic and GABAergic mechanisms

The aim of this study was to investigate the sleep-promoting effects of corn leaf extract (UP165) and its active component 6-methoxybenzoxazolinone (6-MBOA), along with the underlying mechanisms in rodent models. Sleep activity in UP165 was measured by measuring sleep duration in the pentobarbital induced sleep model, and sleep quality was evaluated through electroencephalogram (EEG) analysis. In addition, the sleep mechanism was analyzed through an in vivo sleep study co-administrated with receptor antagonists. The administrations of both UP165 and 6-MBOA effectively increased sleep duration, demonstrating a 3-fold increase sleep time at 100 mg/kg UP165 and a 2.3-fold increase at 280 μg/kg 6-MBOA compared to those of the control group. The sleep-promoting effect of UP165 was also observed in the caffeine-induced insomnia model, resulting in a 71.6% increase in sleep duration. The UP165-mediated increase in sleep time was attributed to enhanced non-rapid eye movement (NREM) sleep, specifically an increase in the δ-wave sleep measured by EEG. Mechanism analysis with co-administration of competitive antagonists in vivo revealed that UP165 and 6-MBOA enhanced sleep duration through binding to gamma-aminobutyric acid type A (GABAA) and melatonin receptors. Oral administration of UP165 for 4 weeks effectively increased both gene expression and protein levels of GABAA, melatonin 1A, and melatonin 1B receptors. High-dose administration of UP165 significantly decreased the blood level of corticosterone, while concurrently increased GABA, serotonin, and melatonin levels in brain. This study highlights the potential of UP165 and 6-MBOA as edible-grade natural ingredients for sleep promotion.

Melatonin and Vascular Function.

The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer's disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology.

Overexpression of oHIOMT results in various morphological, anatomical, physiological and molecular changes in switchgrass.

Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions, but exerts contrasting effects on plants owing to concentration differences. Hydroxyindole O-methyltransferase (HIOMT), which catalyzes the last step of melatonin synthesis, plays a crucial role in this context. Transgenic switchgrass overexpressing oHIOMT with different melatonin levels displayed distinct morphological changes in a concentration-dependent manner. In this study, we divided the transgenic switchgrass into two groups: melatonin-moderate transgenic (MMT) plants and melatonin-rich transgenic (MRT) plants. To determine the concentration-dependent effect of melatonin on switchgrass growth and stress resistance, we conducted comparative morphological, physiological, omics and molecular analyses between MMT, MRT and wild-type (WT) plants. We found that oHIOMT overexpression, with moderate melatonin levels, was crucial in regulating switchgrass growth through changes in cell size rather than cell number. Moderate levels of melatonin were vital in regulating carbon fixation, stomatal development and chlorophyll metabolism. Regarding salt tolerance, melatonin with moderate levels activated numerous defense (e.g. morphological characteristics, anatomical structure, antioxidant enzymatic properties, non-enzymatic capacity and Na+/K+ homeostasis). Additionally, moderate levels of oHIOMT overexpression were sufficient to increase lignin content and alter monolignol compositions with an increase in the S/G lignin ratio. Taken together, oHIOMT overexpression in switchgrass with different melatonin levels resulted in morphological, anatomical, physiological and molecular changes in a concentration-dependent manner, which characterized by stimulation at low doses and inhibition at high doses. Our study presents new ideas and clues for further research on the mechanisms of the concentration-dependent effect of melatonin.