Medical Studies on Melatonin

Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder

2021-02 Lalanne S, Fougerou-Leurent C, Anderson GM, Schroder CM, Nir T, Chokron S, Delorme R, Claustrat B, Bellissant E, Kermarrec S, Franco P, Denis L, Tordjman S

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study.

Melatonin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-related Diseases

2021-02 Xie WQ, Chen SF, Tao XH, Zhang LY, Hu PW, Pan WL, Fan YB, Li YS

Cartilage is a relatively simple connective tissue that plays a variety of roles in the human body, including joint support and protection, load bearing of the intervertebral discs, joint lubrication, formation of the external structure of the ears and nose and support of the trachea. The maintenance of cartilage homeostasis is therefore crucial. Cartilage-related diseases are difficult to diagnose and treat because their molecular and pathological mechanisms are not fully understood.

Role of Melatonin on Virus-Induced Neuropathogenesis-A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection.

2021-01 Wongchitrat P, Shukla M, Sharma R, Govitrapong P, Reiter RJ

Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19

2020-10 Zhou Y, Hou Y, Shen J, Kallianpur A, Zein J, Culver DA, Farha S, Comhair S, Fiocchi C, Gack MU, Mehra R, Stappenbeck T, Chan T, Eng C, Jung JU, Jehi L, Erzurum S, Cheng F

The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations.

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

2020-09 Tan DX, Hardeland R

Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen's spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution.

Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19

2020-09 El-Missiry MA, El-Missiry ZMA, Othman AI

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages.

Structural and physico-chemical evaluation of melatonin and its solution-state excited properties, with emphasis on its binding with novel coronavirus proteins

2020-08 Al-Zaqri N, Pooventhiran T, Alsalme A, Warad I, John AM, Thomas R

Melatonin is a natural hormone from the pineal gland that regulates the sleep-wake cycle. We examined the structure and physico-chemical properties of melatonin using electronic structure methods and molecular-mechanics tools. Density functional theory (DFT) was used to optimise the ground-state geometry of the molecule from frontier molecular orbitals, which were analysed using the B3LYP functional.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment

2020-08 Martín Giménez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level.

Melatonin Suppresses Renal Cortical Fibrosis by Inhibiting Cytoskeleton Reorganization and Mitochondrial Dysfunction through Regulation of miR-4516

2020-07 Yoon YM, Go G, Yun CW, Lim JH, Lee JH, Lee SH

Renal fibrosis, a major risk factor for kidney failure, can lead to chronic kidney disease (CKD) and is caused by cytoskeleton reorganization and mitochondrial dysfunction. In this study, we investigated the potential of melatonin treatment to reduce renal fibrosis by recovering the cytoskeleton reorganization and mitochondrial dysfunction.

Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

2020-07 Hazra S, Chaudhuri AG, Tiwary BK, Chakrabartia N

The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19.

Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?

2020-06 Dominguez-Rodriguez A, Abreu-Gonzalez P, Marik PE, Reiter RJ 

The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin.

Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series

2020-06 Castillo RR, Quizon GRA, Juco MJM, Roman ADE, de Leon DG, Punzalan FER, Guingon RBL, Morales DD, Tan DX, Reiter RJ

Treatment for coronavirus disease 2019 (COVID19) pneumonia remains empirical and the search for therapies that can improve outcomes continues. Melatonin has been shown to have anti-inflammatory, antioxidant, and immune-modulating effects that may address key pathophysiologic mechanisms in the development and progression of acute respiratory distress syndrome (ARDS), which has been implicated as the likely cause of death in COVID19.

Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients With Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.

2020-05 Xu L, Yu H, Sun H, Hu B, Geng Y

Alzheimer's disease (AD) is a degenerative disease that is characterized by massive neuron devastations in the hippocampus and cortex. Mild cognitive impairment (MCI) is the transitory stage between normality and AD dementia. This study aimed to investigate the melatonin induced effects on the lamina cribrosa thickness (LCT) of patients with MCI.

Can melatonin reduce the severity of COVID-19 pandemic?

2020-04 Shneider A, Kudriavtsev A, Vakhrusheva A

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks.

Clinical Impact of Melatonin on Breast Cancer Patients Undergoing Chemotherapy; Effects on Cognition, Sleep and Depressive Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

2020-04 Palmer ACS, Zortea M, Souza A, Santos V, Biazús JV, Torres ILS, Fregni F, Caumo W

This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment.

Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1/miR-141-mediated NLRP3 inflammasome and TGF-β1/Smads signaling in diabetic cardiomyopathy.

2020-04 Che H, Wang Y, Li H, Li Y, Sahil A, Lv J, Liu Y, Yang Z, Dong R, Xue H, Wang L

Melatonin is a hormone produced by the pineal gland, and it has extensive beneficial effects on various tissue and organs; however, whether melatonin has any effect on cardiac fibrosis in the pathogenesis of diabetic cardiomyopathy (DCM) is still unknown.

Antioxidant and Anti-Inflammatory Properties of Melatonin in Patients With Type 2 Diabetes Mellitus With Periodontal Disease Under Non-Surgical Periodontal Therapy: A Double-Blind, Placebo-Controlled Trial.

2020-03 Zare Javid A, Hosseini SA, Gholinezhad H, Moradi L, Haghighi-Zadeh MH, Bazyar H

The imbalance between pro-oxidant and antioxidant systems often leads to further oxidative damage in the pathogenesis of both diabetes and periodontal disease. This study aimed to investigate the antioxidant and anti-inflammatory properties of melatonin in type 2 diabetes mellitus (T2DM) patients with periodontal disease (PD) under non-surgical periodontal therapy (NSPT).

Melatonin a Promising Candidate for DNA Double-Stranded Breaks Reduction in Patients Undergoing Abdomen-Pelvis Computed Tomography Examinations.

2020-03 Eskandari A, Mahmoudzadeh A, Shirazi A, Esmaely F, Carnovale C, Cheki M

Cancer incidence is 24% greater in children and young adults exposed to Computed Tomography (CT) scans than those unexposed. Non-repair of ionizing radiation-induced DNA double-Strand Breaks (DSBs) can initiate carcinogenesis. In the present study, we aimed to investigate the radioprotective potential of melatonin against DSBs in peripheral blood lymphocytes of patients undergoing the abdomen-pelvis CT examinations.

Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.

2020-02 Kaur S, Teoh AN, Shukri NHM, Shafie SR, Bustami NA, Takahashi M, Lim PJ, Shibata S

Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes.

Effect of Melatonin Supplementation in Combination With Neoadjuvant Chemotherapy to miR-210 and CD44 Expression and Clinical Response Improvement in Locally Advanced Oral Squamous Cell Carcinoma: A Randomized Controlled Trial.

2020-02 Kartini D, Taher A, Panigoro SS, Setiabudy R, Jusman SW, Haryana SM, Abdullah M, Rustamadji P, Purwanto DJ, Sutandyo N, Suroyo I, Siregar BH, Maruli H, Sungkar S

Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment.

The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial.

2019-12 Madsen MT, Zahid JA, Hansen CH, Grummedal O, Hansen JR, Isbrand A, Andersen UO, Andersen LJ, Taskiran M, Simonsen E, Gögenur I

Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression.

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.

2019-12 Chuffa LGA, Lupi LA, Cucielo MS, Silveira HS, Reiter RJ, Seiva FRF

The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the "receptivity window". Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage.

Reduced melatonin synthesis in pregnant night workers: Metabolic implications for offspring.

2019-11 Nehme PA, Amaral F, Lowden A, Skene DJ, Cipolla-Neto J, Moreno CRC

Several novel animal studies have shown that intrauterine metabolic programming can be modified in the event of reduced melatonin synthesis during pregnancy, leading to glucose intolerance and insulin resistance in the offspring. It is therefore postulated that female night workers when pregnant may expose the offspring to unwanted health threats.

Melatonin has profound effects on mitochondrial dynamics in myocardial ischaemia/reperfusion.

2019-11 Dube K, Dhanabalan K, Salie R, Blignaut M, Huisamen B, Lochner A

Research focus recently shifted to mitochondrial dynamics and the role of fusion and fission in cardioprotection. The aim of this study was to evaluate (i) the function and dynamics of mitochondria isolated from hearts exposed to ischaemia/reperfusion (I/R) (ii) the effects of melatonin, a powerful cardioprotectant, on mitochondrial dynamics in I/R.

Infusion of Melatonin Into the Paraventricular Nucleus Ameliorates Myocardial Ischemia-Reperfusion Injury by Regulating Oxidative Stress and Inflammatory Cytokines.

2019-10 Yang JB, Kang YM, Zhang C, Yu XJ, Chen WS

Melatonin, the receptors for which are abundant in the hypothalamic paraventricular nucleus (PVN), can protect the heart from myocardial ischemia-reperfusion (MI/R) injury. The aim of this study was to determine whether the infusion of melatonin into the PVN protects the heart from MI/R injury by suppressing oxidative stress or regulating the balance between proinflammatory cytokines and anti-inflammatory cytokines in MI/R rats.

Melatonin for prevention of placental malperfusion and fetal compromise associated with intrauterine inflammation-induced oxidative stress in a mouse model.

2019-10 Lee JY, Li S, Shin NE, Na Q, Dong J, Jia B, Jones-Beatty K, McLane MW, Ozen M, Lei J, Burd I

Melatonin has been shown to reduce oxidative stress and mitigate hypercoagulability. We hypothesized that maternally administered melatonin may reduce placental oxidative stress and hypercoagulability associated with exposure to intrauterine inflammation (IUI) and consequently improve fetoplacental blood flow and fetal sequelae.

Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment.

2019-08 Espino J, Macedo M, Lozano G, Ortiz Á, Rodríguez C, Rodríguez AB, Bejarano I

Unexplained infertility occurs when common causes for a couple's inability to conceive have been excluded. Although origins of idiopathic infertility are still unclear, factors, such as an altered oxidative balance, are believed to be involved. Melatonin is an outstanding antioxidant reportedly present in the follicular fluid (FF), which has been suggested as a useful tool in the management of human fertility.

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

2019-07 Dodda BR, Bondi CD, Hasan M, Clafshenkel WP, Gallagher KM, Kotlarczyk MP, Sethi S, Buszko E, Latimer JJ, Cline JM, Witt-Enderby PA, Davis VL

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer.

Melatonin MT1 receptor as a novel target in neuropsychopharmacology: MT1 ligands, pathophysiological and therapeutic implications, and perspectives.

2019-06 Comai S, Lopez-Canul M, De Gregorio D, Posner A, Ettaoussi M, Guarnieri FC, Gobbi G

Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT1 and MT2, regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT1/MT2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders.

Melatonin profiles during the third trimester of pregnancy and health status in the offspring among day and night workers: A case series.

2019-04 Nehme PA, Amaral FG, Middleton B, Lowden A, Marqueze E, França-Junior I, Antunes JLF, Cipolla-Neto J, Skene DJ, Moreno CRC

Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus.

Melatonin is a biomarker of circadian dysregulation and is correlated with major depression and fibromyalgia symptom severity.

2019-01 Caumo W, Hidalgo MP, Souza A, Torres ILS, Antunes LC

This study compared urinary 6-sulfatoxymelatonin (aMT6s) over 24 hours among fibromyalgia (FM), major depression disorder (MDD), and healthy control (HC) groups, and examined whether rhythm is correlated with depressive symptoms. To answer this question we compared the rhythm of urinary aMT6s secretion among each group in four time series: morning (06:00-12:00 hours), afternoon (12:00-18:00 hours), evening (18:00-24:00 hours), and night (24:00-06:00 hours). In the FM subjects, we assessed if the rhythm of urinary aMT6s secretion is associated with pain severity, sleep quality, number of trigger points (NTPs), and the pain pressure threshold (PPT).

Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia.

2018-10 Hobson SR, Gurusinghe S, Lim R, Alers NO, Miller SL, Kingdom JC, Wallace EM

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine whether melatonin could be a useful adjuvant therapy.

Serum Levels of Melatonin and Oxidative Stress Markers and Correlation between Them in Infertile Men.

2013-11 Soleimani Rad S, Abbasalizadeh S, Ghorbani Haghjo A, Sadagheyani M, Montaseri A, Soleimani Rad J

Infertility is the problem of 15% of young couples in different societies. One of the factors that could affect fertility is oxidative stress. Therefore, the aim of the present study is to investigate the level of Melatonin, a free radical scavenger, and its correlation with oxidative biomarkers in infertile men.

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