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Biogerontology Oct 2022Melatonin is a tryptophan-derived ancestral molecule evolved in bacteria. According to the endosymbiotic theory, eukaryotic cells received mitochondria, plastids, and... (Review)
Review
Melatonin is a tryptophan-derived ancestral molecule evolved in bacteria. According to the endosymbiotic theory, eukaryotic cells received mitochondria, plastids, and other organelles from bacteria by internalization. After the endosymbiosis, bacteria evolved into organelles and retained their ability of producing melatonin. Melatonin is a small, evolutionarily conserved indole with multiple receptor-mediated, receptor-dependent, and independent actions. Melatonin's initial function was likely a radical scavenger in bacteria that's why there was high intensity of free radicals on primitive atmosphere in the ancient times, and hormetic functions of melatonin, which are effecting through the level of gene expression via prooxidant and antioxidant redox pathways, are developed in throughout the eukaryotic evolution. In the earlier stages of life, endosymbiotic events between mitochondria and other downstream organelles continue with mutual benefits. However, this interaction gradually deteriorates as a result of the imperfection of both mitochondrial and extramitochondrial endosymbiotic crosstalk with the advancing age of eukaryotic organisms. Throughout the aging process melatonin levels tend to reduce and as a manifestation of this, many symptoms in organisms' homeostasis, such as deterioration in adjustment of cellular clocks, are commonly seen. In addition, due to deterioration in mitochondrial integrity and functions, immunity decreases, and lower levels of melatonin renders older individuals to be more susceptible to impaired redox modulation and age-related diseases. Our aim in this paper is to focus on the several redox modulation mechanisms in which melatonin signaling has a central role, to discuss melatonin's gerontological aspects and to provide new research ideas with researchers.
Topics: Aging; Antioxidants; Free Radicals; Humans; Melatonin; Signal Transduction
PubMed: 35895186
DOI: 10.1007/s10522-022-09981-y -
International Journal of Molecular... Mar 2017Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver... (Review)
Review
Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action.
Topics: Animals; Apoptosis; Autophagy; Humans; Liver; Liver Diseases; Melatonin
PubMed: 28333073
DOI: 10.3390/ijms18040673 -
Current Pharmaceutical Design 2018Circadian rhythm disruption underlies the pathophysiology of psychiatric disorders, especially depression. Both pharmacological and non-pharmacological strategies... (Review)
Review
BACKGROUND
Circadian rhythm disruption underlies the pathophysiology of psychiatric disorders, especially depression. Both pharmacological and non-pharmacological strategies affecting endogenous circadian rhythms have been developed with specificity to alter the circadian dysfunction. The current management strategy with antidepressants is far from being satisfactory in addressing this issue. In recent years, attempts at discovering new antidepressants focused on a melatonergic system which is known to be altered in depression have led to a potential option for treatment of depression.
METHODS
We reviewed all recently published relevant articles on melatonin and its analogues to look for their implication in the treatment of circadian rhythm disruption and depression.
RESULTS
Melatonin, a pleiotropic regulator molecule and its analogues (ramelteon, agomelatine, TIK-301, Neu- P11 and tasimelteon) have been observed to resynchronize the circadian rhythm and some were said to alleviate depressive symptoms in depressed subjects.
CONCLUSION
This review focuses on substantial advances in the melatonin-based chronobiologic intervention and its responses in the treatment of depression.
Topics: Circadian Rhythm; Depressive Disorder; Humans; Melatonin
PubMed: 30073921
DOI: 10.2174/1381612824666180803112304 -
Current Pharmaceutical Design 2016Melatonin and the following approved or investigational synthetic melatoninergic agonists are compared with regard to half-life, receptor affinity, metabolism and... (Review)
Review
Melatonin and the following approved or investigational synthetic melatoninergic agonists are compared with regard to half-life, receptor affinity, metabolism and additional properties: TIK-301, piromelatine, GG-012, AH-001, AH-017, agomelatine, ramelteon, GR 196429, MA-2, tasimelteon, UCM765, and UCM924. Apart from restrictions from the respective approvals, theoretical limits of treatment are outlined as they result from chronobiological, genetic, epigenetic, degenerative or toxicological considerations. Melatoninergic agonists have been shown to reliably entrain circadian rhythms, if chronobiological phase response rules are followed. This allows the treatment of dysphased rhythms, circadian rhythm sleep disorders, and forms of depression with an etiology of circadian dysfunction, such as bipolar disorder and seasonal affective disorders. Entrainment and induction of sleep onset requires only short actions, with low doses of immediate-release melatonin likely to be sufficient. However, sleep maintenance is poorly supported by any of the agonists, despite statistically demonstrable effects. The combinations of melatoninergic properties with the inhibition of 5-HT2C receptors, as in agomelatine and TIK-30, may result in moderate direct antidepressive actions. Other limits of a successful treatment can arise from genetic or epigenetic silencing of melatonin receptor genes, perhaps also from imbalances between parallel signaling pathways in receptor mutants, and from neurodegeneration, especially in the suprachiasmatic nucleus. Variants of circadian clock genes cause rhythm deviations that may be corrected by melatoninergic treatment, provided that the spontaneous oscillation period is not beyond the entrainment range. Caveats concerning melatonin's roles as an immune modulator and in certain pathologies, such as Parkinson's disease, as well as toxicological considerations for agonists and their metabolites are also addressed.
Topics: Acetamides; Animals; Humans; Indoles; Melatonin; Memory Disorders; Mental Disorders; Pyrans; Receptors, Melatonin
PubMed: 25248806
DOI: 10.2174/1381612822666151214125543 -
Reviews in the Neurosciences Jul 2019Melatonin (N-acetyl-5-methoxytryptamine) is a naturally synthesized hormone secreted from the pineal gland in a variety of animals and is primarily involved in the... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine) is a naturally synthesized hormone secreted from the pineal gland in a variety of animals and is primarily involved in the regulation of the circadian rhythm, which is the natural cycle controlling sleep in organisms. Melatonin acts on specific receptors and has an important role in overall energy metabolism. This review encompasses several aspects of melatonin activity, such as synthesis, source, structure, distribution, function, signaling and its role in normal physiology. The review highlights the cellular signaling and messenger systems involved in melatonin's action on the body and their wider implications, the distribution and diverse action of different melatonin receptors in specific areas of the brain, and the pharmacological agonists and antagonists that have specific action on these melatonin receptors. This review also incorporates the antitumor effects of melatonin in considerable detail, emphasizing on melatonin's role as an adjuvant therapeutic agent in glioma treatment. We conclude that the diminishing levels of melatonin have significant debilitating effects on normal physiology and can also be associated with malignant conditions such as glioma. Based on the review of the available evidence, our study provides a broad platform for a better understanding of the specific roles of melatonin and serves as a starting point for further investigation into the therapeutic effect of melatonin in glioma as an adjuvant therapeutic agent.
Topics: Animals; Antineoplastic Agents; Antioxidants; Brain Neoplasms; Glioma; Humans; Melatonin; Signal Transduction
PubMed: 30645197
DOI: 10.1515/revneuro-2018-0041 -
Medecine Sciences : M/S Jan 2022Melatonin is a naturally occurring molecule derived from tryptophan. Melatonin is a key player in relaying the circadian rhythm between our environment and our body. It... (Review)
Review
Melatonin is a naturally occurring molecule derived from tryptophan. Melatonin is a key player in relaying the circadian rhythm between our environment and our body. It has also a key role in rhythming the seasons (more production during long nights and less during short ones) as well as in the reproduction cycles of the mammals. Melatonin is often and surprisingly presented as a molecule with multiple therapeutic properties that can fix (or help to fix) many health issues, such as diseases (cancer, ageing, virus-induced affections including COVID-19, etc…) or toxicological situations (metals, venoms, chemical such as adriamycin [doxorubicin], methotrexate or paclitaxel). The mechanistics behind those wonders is still missing and this is puzzling. In the present commentary, the main well-established biological properties are presented and briefly discussed with the aim of delineating the borders between facts and wishful thinking.
Topics: Animals; Circadian Rhythm; Communication; Humans; Melatonin; Reproducibility of Results; Seasons; COVID-19 Drug Treatment
PubMed: 35060893
DOI: 10.1051/medsci/2021115 -
International Journal of Molecular... May 2023(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may...
(1) The vicious cycle of innate immune response and reactive oxygen species (ROS) generation is an important pathological process of osteoarthritis (OA). Melatonin may be a new hope for the treatment of OA because of its antioxidant capacity. However, the mechanism of melatonin in the treatment of OA is still not completely clear, and the physiological characteristics of articular cartilage make melatonin unable to play a long-term role in OA. (2) The effects of melatonin on ROS and the innate immune response system in OA chondrocytes and the therapeutic effect in vivo were evaluated. Then, a melatonin-loaded nano-delivery system (MT@PLGA-COLBP) was prepared and characterized. Finally, the behavior of MT@PLGA-COLPB in cartilage and the therapeutic effect in OA mice were evaluated. (3) Melatonin can inhibit the activation of the innate immune system by inhibiting the TLR2/4-MyD88-NFκB signal pathway and scavenging ROS, thus improving cartilage matrix metabolism and delaying the progression of OA in vivo. MT@PLGA-COLBP can reach the interior of cartilage and complete the accumulation in OA knee joints. At the same time, it can reduce the number of intra-articular injections and improve the utilization rate of melatonin in vivo. (4) This work provides a new idea for the treatment of osteoarthritis, updates the mechanism of melatonin in the treatment of osteoarthritis, and highlights the application prospect of PLGA@MT-COLBP nanoparticles in preventing OA.
Topics: Mice; Animals; Melatonin; Reactive Oxygen Species; Delayed-Action Preparations; Osteoarthritis; Chondrocytes; Cartilage, Articular; Polylactic Acid-Polyglycolic Acid Copolymer; Nanoparticles
PubMed: 37240086
DOI: 10.3390/ijms24108740 -
International Journal of Molecular... May 2024Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role... (Review)
Review
Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.
Topics: Melatonin; Humans; Administration, Topical; Antioxidants; Animals; Skin Aging; Clinical Studies as Topic; Skin; Skin Diseases
PubMed: 38791203
DOI: 10.3390/ijms25105167 -
International Journal of Molecular... May 2024While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in... (Review)
Review
While primarily produced in the pineal gland, melatonin's influence goes beyond its well-known role in regulating sleep, nighttime metabolism, and circadian rhythms, in the field of chronobiology. A plethora of new data demonstrates melatonin to be a very powerful molecule, being a potent ROS/RNS scavenger with anti-inflammatory, immunoregulatory, and oncostatic properties. Melatonin and its metabolites exert multiple beneficial effects in cutaneous and systemic aging. This review is focused on the neuroprotective role of melatonin during aging. Melatonin has an anti-aging capacity, retarding the rate of healthy brain aging and the development of age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. Melatonin, as well as its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), can reduce oxidative brain damage by shielding mitochondria from dysfunction during the aging process. Melatonin could also be implicated in the treatment of neurodegenerative conditions, by modifying their characteristic low-grade neuroinflammation. It can either prevent the initiation of inflammatory responses or attenuate the ongoing inflammation. Drawing on the current knowledge, this review discusses the potential benefits of melatonin supplementation in preventing and managing cognitive impairment and neurodegenerative diseases.
Topics: Melatonin; Humans; Brain; Aging; Animals; Neurodegenerative Diseases; Neuroprotection; Neuroprotective Agents; Oxidative Stress; Kynuramine
PubMed: 38791160
DOI: 10.3390/ijms25105122 -
Frontiers in Immunology 2022The therapeutic outcomes of exosome-based therapies have greatly exceeded initial expectations in many clinically intractable diseases due to the safety, low toxicity,... (Review)
Review
The therapeutic outcomes of exosome-based therapies have greatly exceeded initial expectations in many clinically intractable diseases due to the safety, low toxicity, and immunogenicity of exosomes, but the production of the exosomes is a bottleneck for wide use. To increase the yield of the exosomes, various solutions have been tried, such as hypoxia, extracellular acidic pH, etc. With a limited number of cells or exosomes, an alternative approach has been developed to improve the efficacy of exosomes through cell pretreatment recently. Melatonin is synthesized from tryptophan and secreted in the pineal gland, presenting a protective effect in pathological conditions. As a new pretreatment method, melatonin can effectively enhance the antioxidant, anti-inflammatory, and anti-apoptotic function of exosomes in chronic kidney disease, diabetic wound healing, and ischemia-reperfusion treatments. However, the current use of melatonin pretreatment varies widely. Here, we discuss the effects of melatonin pretreatment on the heterogeneity of exosomes based on the role of melatonin and further speculate on the possible mechanisms. Finally, the therapeutic use of exosomes and the usage of melatonin pretreatment are described.
Topics: Anti-Inflammatory Agents; Antioxidants; Exosomes; Melatonin; Tryptophan
PubMed: 36189281
DOI: 10.3389/fimmu.2022.933736