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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 -
La Revue Du Praticien Mar 2024PHARMACOTHERAPIES FOR INSOMNIA. The first line of treatment in adult chronic insomnia is cognitive behavioral therapy (CBT). However, its difficult accessibility limited...
PHARMACOTHERAPIES FOR INSOMNIA. The first line of treatment in adult chronic insomnia is cognitive behavioral therapy (CBT). However, its difficult accessibility limited its use and medications are still often prescribed. Considering the drugs with marketing authorization, Z-drugs (zolpidem and zopiclone) if taken at the right hour and dosage promote sleep initiation and have less deleterious effects than benzodiazepines, especially the long-acting ones which should be avoided. This class of drugs cannot be prescribed longer than 28 days. Some antihistaminic licensed drugs are authorized as hypnotics, with a low proof of efficacy and a risk of adverse event as sedation and somnolence the next day. Their prescription should be avoided in old subjects. Some clinicians used antidepressant sedative medications, at low dosage, as hypnotic drugs but "off label", outside authorization. Now melatonin, an endogenous synchronizer of biologic rhythms, has obtained the authorization for the treatment of insomniac troubles, in subjects of at least 55 years old, in its slow- release formula, replacing the physiological decline of this hormone with aging. Melatonin is not a hypnotic, but has soporific properties, inducing sleep, improving sleep efficacy, sometimes sleep duration and morning alertness. When discontinued, it induced no withdrawal syndrome. It has shown no risk of abuse potential and no deleterious side-effects, if used at the right dose and in the absence of hepatic interaction with other compounds. Finally, a new class of hypnotics, "the orexin antagonists" has its first representative on the French market: daridorexant. The place of these molecules in the therapeutic strategy for chronic insomnia needs to be clarified.
Topics: Adult; Humans; Middle Aged; Sleep Initiation and Maintenance Disorders; Melatonin; Hypnotics and Sedatives; Benzodiazepines; Sleep; Antidepressive Agents
PubMed: 38551874
DOI: No ID Found -
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 -
Revista Da Associacao Medica Brasileira... 2023
Topics: Humans; Female; Breast Neoplasms; Melatonin; Estrogens; Breast
PubMed: 37792874
DOI: 10.1590/1806-9282.6910EDI -
Microbiological Research Nov 2023Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic...
BACKGROUND AND PURPOSE
Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear.
EXPERIMENTAL APPROACH
C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation.
KEY RESULTS
We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above.
CONCLUSION AND IMPLICATIONS
Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.
Topics: Animals; Mice; Humans; Mice, Inbred C57BL; Melatonin; STAT3 Transcription Factor; Caco-2 Cells; Dysbiosis; Gastrointestinal Diseases; Cytokines; Hypoxia
PubMed: 37659335
DOI: 10.1016/j.micres.2023.127480 -
Sleep Medicine Aug 2024Background Melatonin use in the pediatric population is on the rise in the United States, where it is available as an over-the-counter and online supplement. There are...
Background Melatonin use in the pediatric population is on the rise in the United States, where it is available as an over-the-counter and online supplement. There are no data regarding the safety and efficacy of melatonin in children less than 2 years old. The aim of this study was to examine various aspects of melatonin use by caregivers of infants and toddlers in the US. Methods Caregiver users of the Nanit baby monitoring system with a child aged 0-36 months were invited to complete an online survey regarding melatonin use, sources of information/recommendations about melatonin, formulations used and reasons for administering melatonin to their child. Participants also completed the Brief Infant Sleep Questionnaire-Revised (BISQ-R). Results A total of 3063 caregivers (1.93%) responded to the survey, of whom 1.7% had ever used melatonin for their child. About half of those caregivers had received a recommendation for melatonin from a source other than a healthcare professional. Caregiver perception of 'sleep as a problem' as assessed by the BISQ-R was not significantly different between those who had or had not used melatonin for their child, and reasons for use included non-supported indications such as sleeping later or promoting "more restful and better sleep". Conclusions The results of this study support mounting concerns regarding the widespread use of melatonin in the US pediatric population, especially given the lack of regulatory oversight and the documented inaccuracy of label claims versus actual melatonin content.
Topics: Humans; Melatonin; Infant; Female; Male; Child, Preschool; Caregivers; Surveys and Questionnaires; Sleep; United States; Infant, Newborn; Adult
PubMed: 38878351
DOI: 10.1016/j.sleep.2024.06.008 -
Molecular and Cellular Endocrinology Oct 2023Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide...
Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide structural support and nutrition to germ cells, we evaluated the effect of melatonin on oxidative state and lactate metabolism in the immature murine TM4 cell line and in immature hamster Sertoli cells. A prooxidant stimulus applied to rodent Sertoli cells expressing MT1/MT2 receptors, increased lipid peroxidation whereas decreased antioxidant enzymes (superoxide dismutase 1, catalase, peroxiredoxin 1) expression and catalase activity. These changes were prevented by melatonin. Furthermore, melatonin stimulated lactate dehydrogenase (LDH) expression/activity via melatonin receptors, and increased intracellular lactate production in rodent Sertoli cells. Interestingly, oral melatonin supplementation in infertile men positively regulated LDHA testicular mRNA expression. Overall, our work provides insights into the potential benefits of melatonin on Sertoli cells contributing to testicular development and the future establishment of a sustainable spermatogenesis.
Topics: Male; Cricetinae; Mice; Animals; Sertoli Cells; Melatonin; Catalase; Antioxidants; Rodentia; Oxidative Stress; Lactates
PubMed: 37516434
DOI: 10.1016/j.mce.2023.112034 -
Journal of Cellular and Molecular... Aug 2023Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be...
Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133 cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133 cells compared to CD133 cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.
Topics: Humans; Cisplatin; Melatonin; Stomach Neoplasms; Cell Line, Tumor; Signal Transduction; Apoptosis; Cell Proliferation
PubMed: 37307404
DOI: 10.1111/jcmm.17809 -
Trends in Molecular Medicine Dec 2023The two monoamines serotonin and melatonin have recently been highlighted as potent regulators of islet hormone secretion and overall glucose homeostasis in the body. In... (Review)
Review
The two monoamines serotonin and melatonin have recently been highlighted as potent regulators of islet hormone secretion and overall glucose homeostasis in the body. In fact, dysregulated signaling of both amines are implicated in β-cell dysfunction and development of type 2 diabetes mellitus (T2DM). Serotonin is a key player in β-cell physiology and plays a role in expansion of β-cell mass. Melatonin regulates circadian rhythm and nutrient metabolism and reduces insulin release in human and rodent islets in vitro. Herein, we focus on the role of serotonin and melatonin in islet physiology and the pathophysiology of T2DM. This includes effects on hormone secretion, receptor expression, genetic variants influencing β-cell function, melatonin treatment, and compounds that alter serotonin availability and signaling.
Topics: Humans; Diabetes Mellitus, Type 2; Melatonin; Serotonin; Insulin; Insulin-Secreting Cells; Glucose
PubMed: 37722934
DOI: 10.1016/j.molmed.2023.08.009 -
European Journal of Pharmacology Oct 2023Atherosclerosis (AS)-associated cardiovascular diseases are predominant causes of morbidity and mortality worldwide. Melatonin, a circadian hormone with...
Atherosclerosis (AS)-associated cardiovascular diseases are predominant causes of morbidity and mortality worldwide. Melatonin, a circadian hormone with anti-inflammatory activity, may be a novel therapeutic intervention for AS. However, the exact mechanism is unclear. This research intended to investigate the mechanism of melatonin in treating AS. Melatonin (20 mg/kg/d) was intraperitoneally administered in a high-fat diet (HFD)-induced AS model using apolipoprotein E-deficient (ApoE) mice for 12 weeks. Immunohistochemical and immunofluorescence analyses, data-independent acquisition (DIA)-based protein profiling, ingenuity pathway analysis (IPA), and western blotting were employed to investigate the therapeutic effects of melatonin in treating HFD-induced AS. An adeno-associated virus (AAV) vector was further used to confirm the antiatherosclerotic mechanism of melatonin. Melatonin treatment markedly attenuated atherosclerotic lesions, induced stable phenotypic sclerotic plaques, inhibited macrophage infiltration, and suppressed the production of proinflammatory cytokines in ApoE mice with HFD-induced AS. Notably, DIA-based quantitative proteomics together with IPA identified S100a9 as a pivotal mediator in the protective effects of melatonin. Moreover, melatonin significantly suppressed HFD-induced S100a9 expression at both the mRNA and protein levels. The overexpression of S100a9 significantly activated the NF-κB signaling pathway and markedly abolished the antagonistic effect of melatonin on HFD-induced vascular inflammation during atherogenesis. Melatonin exerts a significant antiatherogenic effect by inhibiting S100a9/NF-κB signaling pathway-mediated vascular inflammation. Our findings reveal a novel antiatherosclerotic mechanism of melatonin and underlie its potential clinical use in modulating AS with good availability and affordability.
Topics: Animals; Mice; Melatonin; NF-kappa B; Atherosclerosis; Apolipoproteins E; Inflammation
PubMed: 37625682
DOI: 10.1016/j.ejphar.2023.175965