Melatonin Group Research Articles

The impact of melatonin on postoperative delirium in geriatric patients after colorectal surgery: a randomized placebo-controlled trial.

The current study was designed to evaluate the role of prophylactic melatonin administration in reducing delirium occurrence in elderly patients undergoing colorectal cancer surgeries. One hundred patients of both genders undergoing elective colorectal cancer surgeries under general anesthesia were randomly allocated into two equal groups. A treatment group of patients (Melatonin group) received five mg of melatonin the night before surgery, twelve hours before the scheduled surgery time, and an additional five mg of melatonin two hours before surgery. The control group of patients received placebo tablets at the same time points. Delirium score, sedation score, pain score, hemodynamics, oxygen saturation, and blood requirements were recorded. Twenty-eight patients (56%) in the control group versus 18 (36%) in the melatonin group developed delirium (P=0.045), OR=2.26, 95% CI: 1.013-5.05. Five patients (18%) in the control group versus six (33%) ‎in the melatonin group developed delirium on discharge from the ‎recovery room (P=0.749), OR=1.22, 95% CI: 0.34-4.31, while 23 patients (82%) in the control group versus ‎‎12 (66%) in the melatonin group developed delirium six hours postoperative (P=0.021), OR=1.705, 95% CI: 1.02-2.81 ‎with higher nursing delirium screening score in the control group 2 (1, 4) versus 1 (0, 2) in the melatonin group (P=0.002), 95% CI: 1.77-2.71. The prophylactic administration of melatonin may decrease the incidence of postoperative delirium in elderly patients undergoing colorectal surgeries under general anesthesia.

Melatonin activates Nrf2/HO-1 signalling pathway to antagonizes oxidative stress-induced injury via melatonin receptor 1 (MT1) in cryopreserved mice ovarian tissue.

Our previous research has shown that melatonin (MLT) can reduce cryopreserved ovarian damage in mice. Yet, the molecular mechanism of MLT protection is still unclear. Some studies have shown that melatonin receptor 1 (MT1) is very important for animal reproductive system. To evaluate whether MLT exerts its protective effect on cryopreserved mice ovarian tissue via MT1, we added antagonist of MT1/MT2 (Luzindor) or antagonist of MT2 (4P-PDOT) to the freezing solution, followed by cryopreservation and thawing of ovarian tissue. The levels of total superoxide dismutase (T-SOD), catalase (CAT), nitric oxide (NO) and malondialdehyde (MDA) were detected. Besides, by using RT-PCR and Western blotting, the expression of Bcl-2, Bax and Nrf2/HO-1 signalling pathway-related proteins was detected. These findings demonstrated that compared with the melatonin group, the addition of Luzindor increased apoptosis, NO and MDA activities, decreased CAT and T-SOD activities and inhibited Nrf2/HO-1 signalling pathway. In conclusion, melatonin can play a protective role in cryopreserved ovarian tissue of mice through MT1 receptor.

Anti-Toxic Principles from Musa Sapientum and Moringa Oleifera Ameliorated Skin Histo-Pathology, Decreased Lipid Peroxidation and Promoted Melatonin/TNF-Alpha/p53-Mediated Apoptosis in Cadmium Chloride-Induced Carcinogenesis in Rats

This study evaluated anticancer potentials of Musa sapientum (MS) and Moringa oleifera (MO) in cadmium chloride (CdCl2)-induced skin and liver carcinogenesis. Musa sapientum fraction-1 (MSF1) and Moringa oleifera fraction-6 (MOF6) were extracted from MS suckers and MO leaves, respectively, using column-chromatography methods. Forty-five adult male rats were randomly divided into 11 groups (n = 5). Cancer-induction was via single intraperitoneal administration of 1.25 mg/kg CdCl2. Groups 1 and 2 received physiological saline and CdCl2 dose, respectively. Groups 3–5 received CdCl2 dose on day 1 but were post-treated on days 15–56 with 15 mg/kg MOF6, 30 mg/kg MOF6 and 10 mg/kg MSF1, respectively. Group 6 received CdCl2dose on day 1 and were post-treated on days 15– 28 with doxorubicin + cisplatin doses. Groups 7–9 received MOF6 dose and MSF1 dose, respectively (days 1–56). Groups 10 and 11 received CdCl2dose on day 1 and were posttreated with 30 mg/kg MOF6 and 10 mg/kg MSF1, respectively (days 1–56). Doxorubicin and extracts doses were administered orally. Skin histo-pathology (haematoxylin and eosin), sera melatonin and tumour necrosis factor-alpha (TNFa) (enzyme linked immunosorbent assays [ELISA]) levels were evaluated. Malondialdehyde (thiobarbituric acid assay) and p53 (ELISA) levels were evaluated in liver homogenates. Data were statistically analysed using ANOVA at p ≤ 0.05. Results showed skin histo-alterations in Group 2, compared with normal skin histology in Groups 1 and 3–11. Statistical analyses showed significant downregulation of p53, non-significant downregulations of malondialdehyde and TNFa, and non-significant upregulation of melatonin in Groups 3–11 compared with Group 2. Overall, post-treatments with MOF6 and MSF1 exhibited possible anticancer potentials of these plants extracts via degrees of amelioration of CdCl2-induced skin histo-pathology and carcinogenesis.

Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model.

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.

Effects of Pinealectomy and Melatonin Supplementation on Elements Metabolism in Rat Testicular Tissue

Objective: The aim of this study was to investigate how pinealectomy and melatonin application affect elements metabolism in rat testicular tissue. Methods: The study was carried out on 32 adult male Spraque-Dawley rats. Animals were divided into 4 equal groups. Group 1: Control, Group 2: Melatonin, Group 3: Pinealectomy, Group 4: Pinealectomy+Melatonin. Group 2 and 4 animals received daily 3mg/kg intraperitoneal (ip) melatonin supplementation for 4 weeks. The pineal glands of Group 3 and 4 animals were removed under general anesthesia. At the end of the applications, testicular tissue samples were taken from the animals sacrificed under general anesthesia. Elemental determinations (µg/gram/tissue) were performed in testicular tissue samples using the atomic emission method. Results: The highest cobalt, molybdenum, nickel, manganese, phosphorus, and sodium levels (p&lt;0.001) and the lowest potassium levels in the testicular tissue were obtained in the pinealectomy group (group 3) (p&lt;0.001). Magnesium and selenium values in testicular tissue were highest in the pinealectomy group (group 3) (p&lt;0.001), and were higher in the pinealectomy+melatonin group (group 4) than ingroup 1 (control) and group 2 (melatonin) (p&lt;0.001). Testicular zinc levels were highest in group 2, where melatonin was administered, and lowest in group 3, which was the pinealectomy group (p&lt;0.001). Conclusion: The findings obtained as a result of the study show that pinealectomy significantly disrupts element metabolism in the testicular tissue of rats, and melatonin supplementation may have a regulatory effect on testicular elemental metabolism.

Efficacy of melatonin in alleviating disorders arising from repeated exposure to sevoflurane in males and females of the Wistar rats during preadolescence

Pediatricians use sevoflurane due to its fast action and short recovery time. However, studies have shown that repeated exposure to anesthesia can affect learning and memory. Melatonin, an indole-type neuroendocrine hormone, has significant anti-inflammatory, and neuroprotective properties. Melatonin’s impact on cognitive behavior in sevoflurane-anesthetized males and females of the Wistar rats during preadolescence was examined in this research. The cognitive function was evaluated by shuttle box and morris water maze tests, while interleukin-10, Catalase (CAT), Malondialdehyde (MDA), and Tumor Necrosis Factor-α (TNF-α) were evaluated using ELISA kits. The expression levels of the apoptosis-linked proteins, Bax, Bcl-2, and caspase-3, were determined using the western blotting technique. The learning and memory latencies of the rats were more significant in the sevoflurane groups than in the control group; however, the latencies were significantly shorter in the sevoflurane and melatonin groups than in the control group. The levels of MDA, TNF-α, Bax, and caspase-3 were significantly higher in the sevoflurane groups than in the control group. We also found that the levels of CAT and Bcl-2 were significantly reduced in the sevoflurane groups compared to the control group. Increasing levels of CAT, Bcl-2, and decreasing levels of MDA, TNF-α, Bax, and caspase-3 in response to melatonin indicate a possible contribution to the recovery from the sevoflurane impairment. Melatonin shows neuroprotective effects in male and female rats with sevoflurane-induced cognitive impairment. This suggests melatonin could be a valuable treatment for learning and memory deficits resulting from repeated exposure to sevoflurane, possibly by controlling apoptosis, oxidative stress, and inflammation.

Melatonin suppresses atherosclerosis by ferroptosis inhibition via activating NRF2 pathway.

Melatonin (MLT), a conserved small indole compound, exhibits anti-inflammatory and antioxidant properties, contributing to its cardioprotective effects. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with atherosclerosis disease risk, and is known as an atherosclerosis risk biomarker. This study aimed to investigate the impact of MLT on Lp-PLA2 expression in the atherosclerotic process and explore the underlying mechanisms involved. Invivo, ApoE-/- mice were fed a high-fat diet, with or without MLT administration, after which the plaque area and collagen content were assessed. Macrophages were pretreated with MLT combined with ox-LDL, and the levels of ferroptosis-related proteins, NRF2 activation, mitochondrial function, and oxidative stress were measured. MLT administration significantly attenuated atherosclerotic plaque progression, as evidenced by decreased plaque area and increased collagen. Compared with those in the high-fat diet (HD) group, the levels of glutathione peroxidase 4 (GPX4) and SLC7A11 (xCT, a cystine/glutamate transporter) in atherosclerotic root macrophages were significantly increased in the MLT group. Invitro, MLT activated the nuclear factor-E2-related Factor 2 (NRF2)/SLC7A11/GPX4 signaling pathway, enhancing antioxidant capacity while reducing lipid peroxidation and suppressing Lp-PLA2 expression in macrophages. Moreover, MLT reversed ox-LDL-induced ferroptosis, through the use of ferrostatin-1 (a ferroptosis inhibitor) and/or erastin (a ferroptosis activator). Furthermore, the protective effects of MLT on Lp-PLA2 expression, antioxidant capacity, lipid peroxidation, and ferroptosis were decreased in ML385 (a specific NRF2 inhibitor)-treated macrophages and in AAV-sh-NRF2 treated ApoE-/- mice. MLT suppresses Lp-PLA2 expression and atherosclerosis processes by inhibiting macrophage ferroptosis and partially activating the NRF2 pathway.

Melatonin promotes hair regeneration by modulating the Wnt/β-catenin signalling pathway.

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/β-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/β-catenin signalling pathway revealed that MLT up-regulated the Wnt/β-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/β-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans.

Mechanism of Salvia miltiorrhiza Bunge extract to alleviate Chronic Sleep Deprivation-Induced cognitive dysfunction in rats

BackgroundBidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PurposeThe purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. MethodsDS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. ResultsWe demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1β, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. ConclusionDS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.

Role of oral melatonin in prevention of postoperative delirium in patients undergoing elective surgery under general anesthesia: A Randomized controlled trial.

Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of 3 mg of melatonin administered the night before surgery. Hundred and sixty-two patients aged 40-80 years posted for various urological and gastrointestinal surgeries under general anesthesia with no preoperative cognitive deficits were randomly distributed equally to melatonin or control groups. In the control group, routine premedication was done with tablet alprazolam (0.25 mg) and ranitidine (150 mg), but in the melatonin group, the patients were given 3 mg melatonin orally the night before surgery along with routine premedication. The CAM scale was used for diagnosis of postoperative delirium. Incidence of delirium was significantly lower in the melatonin group, 23.5%, 8.6%, and 2.5% at 6, 24, and 48 hours, respectively, and the corresponding mean (SD) values of CAM scores were 1.37 (1.30), 1.07 (1.03), and 0.69 (0.80). In contrast, the incidence of delirium was 46.9%, 30.9%, and 16% at 6, 24, and 48 hours, respectively, in the control group. There was a significant reduction in anxiety, a lower incidence of cognitive dysfunction (i.e., MoCA score <26), and improvement in sleep quality in the melatonin group at 6, 24, 48, and 72 hours after the surgical intervention. The generalized estimating equations model (GEE) model was used to study change in MoCA and CAM scores over time between the two groups, and it showed a significant interaction between time and treatment groups (P < 0.001). Melatonin premedication reduced incidence of postoperative delirium and cognitive dysfunction and was associated with better sleep quality and anxiolysis.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

The Effect of Melatonin on Reducing the Frequency and Severity of Migraine Attacks: A Double-Blind, Randomized Clinical Trial.

There is no definite recommendation for melatonin supplementation in episodic migraine. This study aimed to evaluate the effect of melatonin on reducing the frequency and severity of migraine attacks. This randomized, double-blind clinical trial was conducted at Golestan Hospital of Ahvaz, Iran, in 2021. A total of 60 patients with episodic migraine were randomly assigned into 2 groups of receiving 3 mg melatonin (intervention group; n=30) or the same dose of placebo (control group; n=30) along with baseline therapy (propranolol 20 mg, BID) for two months. The attack frequency, attack duration, attack severity (based on VAS), the number of analgesic intakes, drug complications, Migraine Disability Assessment score (MIDAS), and Pittsburgh sleep quality index (PSQI) were evaluated at baseline and in the first, second, third, and fourth months of follow-up. The independent t test, chi-square, and analysis of variance (ANOVA) with repeated measures were used to compare variables between the two groups. In both groups, the frequency, duration, and severity of attacks, taking analgesics, MIDAS, and PSQI scores during follow-up decreased significantly (P<0.001). After treatment, the mean frequency (P=0.032) and duration of attacks (P=0.001), taking analgesic (P<0.001), and MIDAS (P<0.001) and PSQI scores (P<0.001) in the melatonin group were lower than placebo. Only the attack severity was not significantly different between the two groups (P=0.126). Side effects were observed in two patients (6.7%) in the melatonin group and one patient (3.3%) in the placebo group (P>0.999). Our study shows that melatonin was more efficacious than the placebo in the reduction of frequency and duration of migraine attacks. It was equally safe as the placebo and might be effective in the preventive treatment of episodic migraine in adults.Trial Registration Number: IRCT20190107042264N5.

Assessing the Premedication Properties of Sublingual Melatonin in Young Women Undergoing Cesarean Section With Spinal Anesthesia: A Double-Blind Randomized Study.

Preoperative anxiety can negatively impact patient outcomes by influencing the intraoperative requirements for anesthetics and analgesics, increasing postoperative pain intensity, and augmenting the need for analgesia. Moreover, it may contribute to higher rates of postoperative morbidity and mortality following certain types of surgery. This study investigates the anxiolytic and sedative properties of sublingual melatonin as a premedication agent in young females undergoing cesarean section under spinal anesthesia. A double-blind, randomized, placebo-controlled trial was conducted in Nasiriyah, Iraq. Eighty females were included, 40 in each group, based on specific inclusion and exclusion criteria. Premedication was administered in the morning, 60 minutes before the procedure. In the melatonin group (M), patients received 10 mg of sublingual melatonin, while the placebo group (P) received placebo premedication. Anxiety and sedation levels were evaluated three times: before taking premedication, five minutes before the insertion of the spinal needle, and one hour postoperatively, using the visual analog scale and Richmond Sedation Scale. The results show a highly significant P-value regarding anxiety levels between the M Group and P Group (p-value < 0.001). There was a significant difference in the median sedation scores between the studied groups at pre-spinal insertion and postoperatively (p-value < 0.001). The mean heart rate in the M Group was significantly lower than in the P Group (p-value = 0.0019). Significant differences were noted in systolic and diastolic blood pressures between the two groups, measured five minutes before and after spinal needle insertion (p-value < 0.001). These findings contribute to understanding the impact of sublingual melatonin as an anxiolytic and sedative premedication agent on patients undergoing elective cesarean sections under spinal anesthesia. Further research is warranted to fully elucidate the benefits and implications of melatonin administration in such procedures.

The Effect of Melatonin on Appendectomy Postoperative Pain: A Randomized Clinical Trial

Background: Melatonin is synthesized from the tryptophan amino acid in the pineal gland. Its role in sleep has been confirmed in other studies. Several studies have also shown the effect of melatonin on postoperative pain and sedation. This study aimed to evaluate the effect of melatonin on postoperative pain in patients undergoing appendectomy. Methods: In a double-blind clinical trial, 64 patients aged 18–50 years with ASA I/II anesthesia class who were candidates for appendectomy with general anesthesia were enrolled. The patients were randomly divided into two groups: melatonin and placebo (32 people in each group). The first group received 6 mg of oral melatonin one hour before sleep, while the second group received a placebo. Before surgery and 2, 12, and 24 hours after surgery, patients’ pain was measured using the Visual Analogue Scale (VAS). The Ramsay sedation score measured the patients’ sedation, and rescue analgesia was measured at the above time points. SPSS software was used to analyze the data, and P-values&lt;0.05 were considered significant. Results: Our study showed that pain levels in the melatonin group were lower at the 2nd, 12th, and 24th hours after the appendectomy surgery than in the placebo group. Sedation rates were not significantly different between the two groups. Analgesic consumption was lower in the melatonin group than in the placebo group. Conclusion: Melatonin can reduce the degree of pain (VAS) after appendectomy.

Melatonin vs. dexmedetomidine for sleep induction in children before electroencephalography.

In children requiring electroencephalography (EEG), sleep recording can provide crucial information. As EEG recordings during spontaneous sleep are not always possible, pharmacological sleep-inducing agents are sometimes required. The aim of the study was to evaluate safety and efficacy of melatonin (Mel) and dexmedetomidine (Dex; intranasal and sublingual application) for sleep induction prior to EEG. In this prospective randomized study, 156 consecutive patients aged 1-19 years were enrolled and randomized by draw into melatonin group (Mel; n = 54; dose: 0.1 mg/kg), dexmedetomidine (Dex) sublingual group (DexL; n = 51; dose: 3 mcg/kg) or dexmedetomidine intranasal group (DexN; n = 51; dose: 3 mcg/kg). We compared the groups in several parameters regarding efficacy and safety and also carried out a separate analysis for a subgroup of patients with complex behavioral problems. Sleep was achieved in 93.6% of participants after the first application of the drug and in 99.4% after the application of another if needed. Mel was effective as the first drug in 83.3% and Dex in 99.0% (p < 0.001); in the subgroup of patients with complex developmental problems Mel was effective in 73.4% and Dex in 100% (p < 0.001). The patients fell asleep faster after intranasal application of Dex than after sublingual application (p = 0.006). None of the patients had respiratory depression, bradycardia, desaturation, or hypotension. Mel and Dex are both safe for sleep induction prior to EEG recording in children. Dex is more effective compared to Mel in inducing sleep, also in the subgroup of children with complex behavioral problems. Dexmedetomidine and Melatonin for Sleep Induction for EEG in Children, NCT04665453.

The Effect of Melatonin on the Expression of H19, MALAT, HOTAIR, THRIL, and NOS Activity in Leishmania major-Infected Macrophages

Background: Leishmania spp. protozoa cause leishmaniasis by infecting macrophages. Long non-coding RNAs (lncRNAs), such as H19, Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT), HOX Antisense Intergenic RNA (HOTAIR), and TNF and HNRNPL Related Immuno-regulatory lncRNA (THRIL), play a role in macrophage polarization and gene regulation. Additionally, leukocytes can synthesize and respond to melatonin, yet the regulatory role of melatonin in Leishmania major-infected macrophages is not well understood. Objectives: This study aimed to assess the impact of melatonin on the expression of lncRNAs like H19, MALAT, HOTAIR, and THRIL, as well as on nitric oxide synthase (NOS) activity in L. major-infected macrophages. Methods: Leishmania major promastigotes and U937 cell lines were cultured. Macrophages were infected with the promastigotes and subsequently treated with melatonin at concentrations of 3, 10, 30, and 100 nM for durations of 4, 24, and 48 hours. The expression levels of the lncRNAs and NOS activity were measured using quantitative Polymerase Chain Reaction (q-PCR) and spectrophotometry, respectively. Results: Melatonin treatment (100 nM) significantly increased the expression of H19 compared to the control after 48 hours (P = 0.002). There was also a significant upregulation of MALAT and HOTAIR in macrophages treated with 3 nM melatonin compared to controls after 48 hours (P = 0.02 and P = 0.003, respectively). Additionally, THRIL expression significantly increased in the melatonin group (10 nM) compared to the control after 4 hours of treatment (P = 0.003). An increase in NOS activity was observed in the melatonin group (100 nM) compared to the control at 4 hours, 24 hours, and 48 hours (P = 0.034, P = 0.011, and P = 0.014, respectively). Conclusions: The findings suggest that melatonin may enhance the expression of H19, THRIL, MALAT, and HOTAIR, as well as NOS activity in macrophages infected with L. major. The upregulation of these lncRNAs by melatonin could potentially improve the macrophages' ability to combat L. major infection.

Efficacy of Melatonin as an Adjunctive Therapy in Hospitalized Patients with Mild to Moderate COVID-19: A Randomized, Double-blind Clinical Trial

Background: Melatonin has proven antioxidant and anti-inflammatory properties that may address the pathophysiology of coronavirus disease 2019 (COVID-19). Therefore, the current study was conducted to evaluate the safety and efficacy of melatonin in COVID-19. Methods: In this single-center, randomized, double-blind, placebo-controlled clinical trial, 96 adults hospitalized with mild to moderate COVID-19 were recruited. The participants were allocated into the melatonin and the placebo groups, randomly (1:1 ratio). Results: The primary outcomes were a reduction in the length of hospital stay, the rate of ICU admissions, intubation/mechanical ventilation, and mortalities within 14 days of starting the treatment compared to the placebo group. After two weeks of follow-up, the blood oxygen saturation and the respiratory rate significantly improved in the melatonin group. C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, creatine phosphokinase, Ferritin, and D-dimer levels were significantly decreased in the melatonin group. Conversely, these markers were considerably increased in the placebo group. These serum marker levels also showed a significant difference in between- group comparison. The comparison of clinical endpoints between the two groups showed no significant difference. Conclusion: This clinical trial study indicated that the combination of oral melatonin tablets and standard treatment could substantially improve blood oxygen saturation and inflammatory factors in mild to moderate hospitalized COVID-19 patients.

Evaluation of the Efficacy of Melatonin in Visual Disturbed Methanol-intoxicated Patients: A Randomized Clinical Trial

Background: This study evaluates the role of oral melatonin in improving vision in methanol toxicity since vision disorders are one of the side effects related to methanol toxicity and assumes the potential effects of melatonin in protecting neurons and optic nerves. Meanwhile, little attention has been paid by researchers to the effect of melatonin in these patients. Methods: A double-blind randomized controlled clinical trial study was conducted on 40 patients diagnosed with methanol toxicity who were referred to Khorshid Hospital of Isfahan City, Iran, from May 2022 to May 2023. These patients were randomly divided into two groups. In the first group (the intervention group), in addition to the usual treatment, the patients were prescribed orally 3 mg of melatonin every morning and 6 mg of melatonin every night for 10 days. In the second group (the control group), in addition to the usual treatment, a placebo was administered similar to the intervention group protocol. Then, the clinical and vision parameters of the patients were evaluated before, during, and after the intervention. Results: The mean pH, PCO2 and HCO3 increased significantly after the intervention compared to the pre-intervention in both groups (P&lt;0.05); however, no significant difference was found between the two groups in any of the two follow-up times (P&gt;0.05). The most common visual complication caused by methadone toxicity was blurred vision with 71.4% and 90% in the melatonin and non-melatonin groups, respectively. Visual complications improved significantly after the intervention compared to the pre-intervention; accordingly, the complete improvement of vision complications in the melatonin group (76.2%) was significantly more than the non-melatonin group (53.3%) (P=0.040). Conclusion: Melatonin improves blurred or snowfield vision in methanol poisoning. Therefore, the administration of melatonin plus routine treatment can be effective in improving vision disorders (blurred or snowfield vision) caused by methanol poisoning.

Anti-aging effect and molecular mechanism of Xiyangshen Sanqi Danshen Granules based on metabolomics and bioinformatics

This study investigated the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules based on metabonomics, network pharmacology, and molecular docking. The aging mice model was induced by intraperitoneal injection of D-galactose(D-gal). Mice were randomly divided into a control group, model group, melatonin group(MT group), and low, medium, and high dose groups of Xiyangshen Sanqi Danshen Granules(XSD-L, XSD-M, and XSD-H). An open-field experiment was conducted, and the expression of cell cycle arrest proteins(p16) and phosphorylated histone family 2A variant(γH2AX) in the brain tissue was detected by immunofluorescence. The expression of interleukin-1β(IL-1β) and interleukin-6(IL-6) in the brain tissue was detected by enzyme-linked immunosorbent assay(ELISA). Metabolomics analysis was performed on the serum of mice in control, model, and XSD-H groups to obtain metabolic processes and metabolites. The effective chemical components and potential targets of Xiyangshen Sanqi Danshen Granules were predicted through network pharmacology, and the network diagram of &quot;drug-effective chemical components-key targets&quot; was constructed. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were carried out, and a protein-protein interaction(PPI) network was constructed to clarify the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules. The results showed that the Xiyangshen Sanqi Danshen Granules could significantly improve the aging degree of D-gal mice, significantly improve the total motion distance and the mean motion speed of D-gal mice, and reduce the rest time. In addition, Xiyangshen Sanqi Danshen Granules could significantly reduce the protein levels of IL-6 and IL-1β and the expression of p16 and γH2AX in D-gal mice. Compared with the model group, 66 differential metabolites(DMs) were significantly up-regulated, and 91 DMs were down-regulated in the XSD-H group. Moreover, four key metabolic pathways(tryptophan metabolism, glycerophospholipid metabolism, pyrimidine metabolism, and lysine degradation) and 16 biomarkers(lysine, tryptophan, indoleacetaldehyde, PCs, LysoPCs, 3-hydroxyanthranilic acid, melatonin, etc) were screened out. 58 main active components and 62 key targets of Xiyangshen Sanqi Danshen Granules were screened by network pharmacology. The GO functional enrichment analysis found the positive regulation of gene expression, drug response, etc. KEGG pathway enrichment screening involved diabetic complications-related AGE-RAGE signaling pathway, hypoxia inducible factor-1 signaling pathway, etc. Through the PPI network and molecular docking, six potential core targets of STAT3, MAPK1, MAPK14, EGFR, FOS, and STAT1 were screened.

Anxiolytic and Sedative Properties of Melatonin Premedication in Pediatrics Undergoing Elective Cardiac Catheterization: A Randomized Placebo Study.

Preoperative anxiety in children has been linked to various postoperative consequences, such as postoperative regressive behavioral issues, extended distress during the recovery period, eating disorders, and bedwetting. The current study aimed to investigate the efficacy of low-dose oral melatonin in alleviating preoperative anxiety among children in the Iraqi population. A randomized, double-blinded comparative study was undertaken, involving children aged four to 14 years scheduled for elective cardiac catheterization under general anesthesia. The study comprised a total of 80 children. The involved individuals were randomly assigned to two groups, each with 40 subjects. Group A received 0.5 mg/kg melatonin as premedication, while Group B received a placebo. The two groups demonstrated similarity in mean age, weight, cardiac disease, and gender distribution. Statistically significant reductions in anxiety scores were observed in the melatonin group compared to the placebo group. Particularly, children administered 0.5 mg/kg melatonin exhibited the most substantial anxiolysis and venipuncture compliance (P < 0.05). Additionally, children who were premedicated with melatonin experienced decreased cognition, maximum sedation, successful parental separation, and psychomotor impairment (P < 0.05). Melatonin demonstrated an effective sedation level without significant side effects, making it a preferred choice due to its efficacy, safety, current availability, and cost-effectiveness compared to other anesthetic agentsused in premedication procedures.