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Osteoporosis International : a Journal... Oct 2023Bone diseases account for an enormous cost burden on health systems. Bone disorders are considered as age-dependent diseases. The aging of world population has... (Review)
Review
PURPOSE
Bone diseases account for an enormous cost burden on health systems. Bone disorders are considered as age-dependent diseases. The aging of world population has encouraged scientists to further explore the most effective preventive modalities and therapeutic strategies to overcome and reduce the high cost of bone disorders. Herein, we review the current evidence of melatonin's therapeutic effects on bone-related diseases.
METHODS
This review summarized evidences from in vitro, in vivo, and clinical studies regarding the effects of melatonin on bone-related diseases, with a focus on the molecular mechanisms. Electronically, Scopus and MEDLINE®/PubMed databases were searched for articles published on melatonin and bone-related diseases from inception to June 2023.
RESULTS
The findings demonstrated that melatonin has beneficial effect in bone- and cartilage-related disorders such as osteoporosis, bone fracture healing, osteoarthritis, and rheumatoid arthritis, in addition to the control of sleep and circadian rhythms.
CONCLUSION
A number of animal and clinical studies have indicated that various biological effects of melatonin may suggest this molecule as an effective therapeutic agent for controlling, diminishing, or suppressing bone-related disorders. Therefore, further clinical studies are required to clarify whether melatonin can be effective in patients with bone-related diseases.
Topics: Animals; Melatonin; Osteoporosis; Circadian Rhythm; Sleep; Bone and Bones
PubMed: 37393580
DOI: 10.1007/s00198-023-06836-1 -
Human & Experimental Toxicology Mar 2021Environmental chemicals and drugs can induce cardiotoxicity, mainly by generating free radicals. Reactive oxygen species play a critical role in the pathogenesis of... (Review)
Review
Environmental chemicals and drugs can induce cardiotoxicity, mainly by generating free radicals. Reactive oxygen species play a critical role in the pathogenesis of cardiac tissue injury. This highlights a need for prevention of cardiotoxicity by scavenging free radicals. Melatonin has been shown to act as a protector against various conditions in which free radicals cause molecular and tissue injury. Some of the mechanisms by which melatonin operates as a free radical scavenger and antioxidant have been identified. The importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in different cardiac pathophysiological disorders have been shown in a variety of model systems. Melatonin continues to attract attention for its potential therapeutic value for cardiovascular toxicity. The therapeutic potential of melatonin in treatment of cardiotoxicities caused by various chemicals along with suggested molecular mechanisms of action for melatonin is reviewed.
Topics: Animals; Cardiotoxicity; Humans; Melatonin
PubMed: 32935581
DOI: 10.1177/0960327120959417 -
Translational Psychiatry Oct 2023Depression is a common chronic psychiatric illness, which is resistant to medical treatments. While melatonin may alleviate certain depression symptoms, evidence for its...
Depression is a common chronic psychiatric illness, which is resistant to medical treatments. While melatonin may alleviate certain depression symptoms, evidence for its efficacy against core symptoms is lacking. Here, we tested a mechanism whereby melatonin rescues the behavioral outcomes of the chronic unpredictable mild stress (CUMS) mouse model of depression. CUMS mice showed depressive behaviors to tail suspension, open field behavior, and sucrose preference test, and cognitive dysfunction in the Morris water maze. Impairments in these measures were relieved by melatonin treatment. Moreover, CUMS mice had impaired glymphatic function across the sleep-wake cycle due to the astrocytic loss and disturbance of circadian regulation of the polarized expression of aquaporin-4 (AQP4) water channels in perivascular astrocytes. EEG results in CUMS mice showed a reduced total sleep time and non-rapid eye movement (NREM) sleep, due to sleep fragmentation in the light phase. CUMS mice lost the normal rhythmic expressions of circadian proteins Per2, Cry2, Bmal1, Clock, and Per1. However, the melatonin treatment restored glymphatic system function and the polarization of AQP4, while improving sleep structure, and rectifying the abnormal expression of Per2, Bmal1, Clock, and Per1 in CUMS mice. Interestingly, Per2 expression correlated negatively with the polarization of AQP4. Further studies demonstrated that Per2 directed the location of AQP4 expression via interactions with the α-dystrobrevin (Dtna) subunit of AQP4 in primary cultured astrocytes. In conclusion, we report a new mechanism whereby melatonin improves depression outcomes by regulating the expression of the circadian protein Per2, maintaining the circadian rhythm of astrocytic AQP4 polarization, and restoring glymphatic function.
Topics: Mice; Animals; Melatonin; Depression; ARNTL Transcription Factors; Circadian Rhythm; Cognitive Dysfunction
PubMed: 37802998
DOI: 10.1038/s41398-023-02614-z -
Rejuvenation Research Dec 2023Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the... (Review)
Review
Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.
Topics: Humans; Animals; Melatonin; Circadian Rhythm; Circadian Clocks; Suprachiasmatic Nucleus; Aging; Mammals
PubMed: 37847148
DOI: 10.1089/rej.2023.0047 -
Molecules (Basel, Switzerland) Nov 2017Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as... (Review)
Review
Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism can be expected upon UV exposure, e.g., in plants and in the human skin. Additionally, melatonin is more strongly nonenzymatically degraded at sites of inflammation. Typical products are several hydroxylated derivatives of melatonin and ¹-acetyl-²-formyl-5-methoxykynuramine (AFMK). Most of these products are also formed by enzymatic catalysis. Considerable taxon- and site-specific differences are observed in the main enzymatic routes of catabolism. Formation of 6-hydroxymelatonin by cytochrome P subforms are prevailing in vertebrates, predominantly in the liver, but also in the brain. In pineal gland and non-mammalian retina, deacetylation to 5-methoxytryptamine (5-MT) plays a certain role. This pathway is quantitatively prevalent in dinoflagellates, in which 5-MT induces cyst formation and is further converted to 5-methoxyindole-3-acetic acid, an end product released to the water. In plants, the major route is catalyzed by melatonin 2-hydroxylase, whose product is tautomerized to 3-acetamidoethyl-3-hydroxy-5-methoxyindolin-2-one (AMIO), which exceeds the levels of melatonin. Formation and properties of various secondary products are discussed.
Topics: Acetylation; Animals; Catalysis; Humans; Hydroxylation; Melatonin; Metabolic Networks and Pathways
PubMed: 29160833
DOI: 10.3390/molecules22112015 -
European Journal of Paediatric... Jul 2022
Topics: Humans; Melatonin
PubMed: 35739037
DOI: 10.1016/j.ejpn.2022.06.008 -
Drug Research Feb 2019Melatonin's pleiotropic actions begin from controlling day/night cycle and hypothalamic/pituitary axes to, for example, vasomotor effects, immunomodulation, antilipid... (Review)
Review
Melatonin's pleiotropic actions begin from controlling day/night cycle and hypothalamic/pituitary axes to, for example, vasomotor effects, immunomodulation, antilipid effects, modulation of endocrine functions, direct and indirect antiapoptotic effects, interference with nitric oxide signaling, other antiexcitatory actions through ion channels and neurotransmitter systems, and most prominently the antioxidant activities which include expression of genes relevant to redox metabolism, including modulation of mitochondrial electron flux. Because of ubiquitous nature of the melatonin receptor, melatonin serves as pleiotropic molecule and its multiplicity of action goes beyond the established antioxidant activities. Melatonin exhibits pleiotropic effects essentially through four different mechanisms: binding to membrane receptors; nuclear receptors; intracellular proteins, and a receptor-independent radical scavenging function. The present review highlights some of the important pleiotropic effects of melatonin in human body.
Topics: Animals; Circadian Clocks; Free Radicals; Humans; Hypothalamo-Hypophyseal System; Melatonin; Receptors, Melatonin; Signal Transduction
PubMed: 30060265
DOI: 10.1055/a-0656-6643 -
Sleep Medicine Clinics Sep 2022This article focuses on melatonin and other melatonin receptor agonists and summarizes their circadian phase shifting and sleep-enhancing properties, along with their... (Review)
Review
This article focuses on melatonin and other melatonin receptor agonists and summarizes their circadian phase shifting and sleep-enhancing properties, along with their associated possible safety concerns. The circadian system and circadian rhythm sleep-wake disorders are described, along with the latest American Academy of Sleep Medicine recommendations for the use of exogenous melatonin in treating them. In addition, the practical aspects of using exogenous melatonin obtainable over the counter in the United States, consideration of the effects of concomitant light exposure, and assessing treatment response are discussed.
Topics: Circadian Rhythm; Humans; Melatonin; Receptors, Melatonin; Sleep; Sleep Disorders, Circadian Rhythm
PubMed: 36150804
DOI: 10.1016/j.jsmc.2022.06.007 -
Current Topics in Medicinal Chemistry 2017Melatonin is an indoleamine with potent multifunctional biological and pharmacological effects, both receptor dependent and receptor-independent effects, including... (Review)
Review
Melatonin is an indoleamine with potent multifunctional biological and pharmacological effects, both receptor dependent and receptor-independent effects, including antioxidant, anticancer, antitumor, anti-inflammatory, anti-aging, anti-diabetic, antiviral, neuroprotective activities. Melatonin mitigates tissue injury via modification of abnormalities in redox status and other biochemical markers. At the molecular level, the biological and pharmacological activities of melatonin are attributed to the inhibition of nuclear factor-κappa beta (NF-κβ), c-Fos over expression and down-regulation of matrix metalloproteinases-3 (MMP-3), which are regulators of pro-inflammatory and pro-fibrotic cytokines. There are numerous scientific reports on the therapeutic potential of melatonin in treatment of asthma, respiratory diseases for infections, chronic obstructive pulmonary disease, lung cancer, pleural cavity diseases, as well as vascular pulmonary disease. In the present communication, we systematically review the therapeutic potential of melatonin in the treatment of respiratory diseases along with its molecular mechanism of actions.
Topics: Animals; Humans; Lung Diseases; Melatonin; Plants
PubMed: 27558675
DOI: 10.2174/1568026616666160824120338 -
International Journal of Molecular... Feb 2023Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective,... (Review)
Review
Melatonin is the main hormone that regulates the sleep cycle, and it is mostly produced by the pineal gland from the amino acid tryptophan. It has cytoprotective, immunomodulatory, and anti-apoptotic effects. Melatonin is also one of the most powerful natural antioxidants, directly acting on free radicals and the intracellular antioxidant enzyme system. Furthermore, it participates in antitumor activity, hypopigmentation processes in hyperpigmentary disorders, anti-inflammatory, and immunomodulating activity in inflammatory dermatoses, maintaining the integrity of the epidermal barrier and thermoregulation of the body. Due predominantly to its positive influence on sleep, melatonin can be used in the treatment of sleep disturbances for those with chronic allergic diseases accompanied by intensive itching (such as atopic dermatitis and chronic spontaneous urticaria). According to the literature data, there are also many proven uses for melatonin in photoprotection and skin aging (due to melatonin's antioxidant effects and role in preventing damage due to DNA repair mechanisms), hyperpigmentary disorders (e.g., melasma) and scalp diseases (such as androgenic alopecia and telogen effluvium).
Topics: Humans; Melatonin; Skin; Antioxidants; Dermatitis, Atopic; Alopecia Areata
PubMed: 36835450
DOI: 10.3390/ijms24044039