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Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies
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Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 20372

Special Issue Editor

Prof. Dr. Juan C. Mayo

E-Mail Website
Guest Editor
Departamento de Morfologia y Biologia Celular, Instituto Universitario Oncologico del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain
Interests: redox regulation; antioxidant enzymes; oxidative stress; prostate cancer; melatonin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Melatonin is the main tryptophan-derived product of the pineal gland, which is responsible for its night release into the blood system, but it is also produced by many tissues and organs. From animal to unicells, to the rest of the animal kingdom, including all vertebrates, its production is always linked to the dark phase during the night. Early studies were focused on the association between the indole and circadian rhythms and photic information. This is still a matter of research, particularly in our non-stop 24h society and the continued exposure to light at night. Many people work at night or in a shift-rotating manner (close to 30% globally). The price we pay is high in terms of an elevated risk in many pathologies, including many types of cancer or metabolic diseases. Therefore, alteration in the pattern of night melatonin release is under intense study.

Additionally, several discoveries in the biology of melatonin have attracted the attention of thousands of scientists, i.e., the antioxidant and anti-inflammatory properties of melatonin, the anti-tumor effects of the indole or the not-well-known impact of melatonin and its receptors variants in type II diabetes. A significant amount of research is needed to answer questions regarding these topics. The clinical consequences of these topics, including the potential therapeutic use of melatonin, also need to be explored.

A new era in melatonin research also begun about two decades ago, when melatonin was discovered in many plant phyla. This has attracted the attention of many plant biologists and has revealed new functions exerted by the indole. Undoubtedly, during the last five years, we have witnessed an increase in plant melatonin research, and a further increase is expected.

For this Special Issue on melatonin, all papers related to any aspect of melatonin physiology, biochemistry, and molecular biology, as well as clinical reports, will be considered. Additionally, studies focused on the role of melatonin in plant biology will be more than welcome

Prof. Dr. Juan C. Mayo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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21 pages, 19233 KiB  
Article
Metabolism of Melatonin Synthesis-Related Indoles in the Turkey Pineal Organ and Its Modification by Monochromatic Light
by Kamila Martyniuk, Maria Hanuszewska and Bogdan Lewczuk
Int. J. Mol. Sci. 2020, 21(24), 9750; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249750 - 21 Dec 2020
Cited by 9 | Viewed by 2108
Abstract
The metabolism of pineal indoles is closely related to alterations in the light and dark phases of a daily cycle. Recent research showed important interspecies differences in the pineal biochemistry, and a strong impact of monochromatic light on many physiological processes in birds. [...] Read more.
The metabolism of pineal indoles is closely related to alterations in the light and dark phases of a daily cycle. Recent research showed important interspecies differences in the pineal biochemistry, and a strong impact of monochromatic light on many physiological processes in birds. Therefore, the aims of study were to characterize the metabolism of melatonin-synthesis indoles in the pineal organ of the domestic turkey, and to determine the changes occurring in this metabolism under the influence of different wavelengths and intensities of light. For this purpose, 3-week-old turkeys were kept under 16 lx white light, or under blue, green, and red light with intensities of 16, 32, and 64 lx during the photophase, and after 7 d were sacrificed at 4 h intervals. The activities of melatonin-synthesizing enzymes and the contents of indoles were measured in the same pineal organ. The results revealed that the activities of tryptophan hydroxylase and arylalkylamine N-acetyltransferase, and the levels of all tryptophan derivatives had significant daily changes in birds kept under each light condition used. The profile of pineal indole metabolism in 4-week-old turkeys was characterized by high-amplitude rhythms in the activity of arylalkylamine N-acetyltransferase and the contents of N-acetylserotonin and melatonin, equal relative amounts of serotonin and 5-hydroxyindoleacetic acid, and higher content of melatonin than N-acetylserotonin. The monochromatic light significantly modified the pineal indole metabolism, and its effects were dependent on the color and intensity of light. Pronounced changes occurred in the level of serotonin synthesis and the daily rhythm course of melatonin synthesis. Full article
(This article belongs to the Special Issue Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies)
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13 pages, 1965 KiB  
Article
Melatonin Protects Cholangiocytes from Oxidative Stress-Induced Proapoptotic and Proinflammatory Stimuli via miR-132 and miR-34
by Ewa Ostrycharz, Urszula Wasik, Agnieszka Kempinska-Podhorodecka, Jesus M. Banales, Piotr Milkiewicz and Malgorzata Milkiewicz
Int. J. Mol. Sci. 2020, 21(24), 9667; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249667 - 18 Dec 2020
Cited by 13 | Viewed by 3406
Abstract
Biosynthesis of melatonin by cholangiocytes is essential for maintaining the function of biliary epithelium. However, this cytoprotective mechanism appears to be impaired in primary biliary cholangitis (PBC). MiR-132 has emerged as a mediator of inflammation in chronic liver diseases. The effect of melatonin [...] Read more.
Biosynthesis of melatonin by cholangiocytes is essential for maintaining the function of biliary epithelium. However, this cytoprotective mechanism appears to be impaired in primary biliary cholangitis (PBC). MiR-132 has emerged as a mediator of inflammation in chronic liver diseases. The effect of melatonin on oxidative stress and bile acid-induced apoptosis was also examined in cholangiocyes overexpressing miR506, as a PBC-like cellular model. In PBC patients the serum levels of melatonin were found increased in comparison to healthy controls. Whereas, in cholangiocytes within cirrhotic PBC livers the melatonin biosynthetic pathway was substantially suppressed even though the expressions of melatonin rate-limiting enzyme aralkylamine N-acetyltransferase (AANAT), and CK-19 (marker of cholangiocytes) were enhanced. In cholangiocytes exposed to mitochondrial oxidative stress melatonin decreased the expression of proapoptotic stimuli (PTEN, Bax, miR-34), which was accompanied by the inhibition of a pivotal mediator of inflammatory response Nf-κB-p65 and the activation of antiapoptotic signaling (miR-132, Bcl2). Similarly, melatonin reduced bile acid-induced proapoptotic caspase 3 and Bim levels. In summary, the insufficient hepatic expression of melatonin in PBC patients may predispose cholangiocytes to oxidative stress-related damage. Melatonin, via epigenetic modulation, was able to suppress NF-κB signaling activation and protect against biliary cells apoptotic signaling. Full article
(This article belongs to the Special Issue Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies)
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18 pages, 5498 KiB  
Article
The Effect of Orally Supplemented Melatonin on Larval Performance and Skeletal Deformities in Farmed Gilthead Seabream (Sparus aurata)
by Kamel Mhalhel, Antonino Germanà, Francesco Abbate, Maria Cristina Guerrera, Maria Levanti, Rosaria Laurà and Giuseppe Montalbano
Int. J. Mol. Sci. 2020, 21(24), 9597; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249597 - 16 Dec 2020
Cited by 7 | Viewed by 3150
Abstract
The gilthead seabream larval rearing in continuous light is common in most Mediterranean hatcheries to stimulate larval length growth and increase food consumption. Several studies have shown that continuous light affects larval development and increases the prevalence of skeletal deformities. Melatonin is a [...] Read more.
The gilthead seabream larval rearing in continuous light is common in most Mediterranean hatcheries to stimulate larval length growth and increase food consumption. Several studies have shown that continuous light affects larval development and increases the prevalence of skeletal deformities. Melatonin is a crucial pineal neurohormone that displays daily secretion patterns, stimulates cell proliferation and embryonic development in Atlantic salmon and zebrafish, and improves osseointegration in mice and humans. However, no studies have examined the effects of orally supplemented melatonin on skeletal deformities in Sparus aurata larvae. We administered exogenous melatonin to gilthead seabream larvae via enriched rotifers and nauplii of Artemia. Exogenous melatonin induced bone deformities and stimulated parathyroid hormone-related protein-coding gene (PTHrP) mRNA expression. In addition to the melatonin-induced PTHrP high expression level, the recorded non coordinated function of skeletal muscle and bone during growth can be the fountainhead of bone deformities. Both myosin light chain 2 (mlc2) and bone gamma-carboxyglutamate protein-coding gene (bglap) expression levels were significantly affected by melatonin administration in an inverse dose–response manner during the exogenous melatonin administration. This is the first study to report the effect of inducing melatonin bone deformities on Sparus aurata larvae reared under ordinary hatchery conditions. Full article
(This article belongs to the Special Issue Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies)
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26 pages, 3851 KiB  
Article
A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma
by Massimo Dal Monte, Maurizio Cammalleri, Rosario Amato, Salvatore Pezzino, Roberta Corsaro, Paola Bagnoli and Dario Rusciano
Int. J. Mol. Sci. 2020, 21(23), 9267; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239267 - 04 Dec 2020
Cited by 17 | Viewed by 2216
Abstract
Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of [...] Read more.
Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health. Full article
(This article belongs to the Special Issue Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies)
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21 pages, 1483 KiB  
Review
Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder
by Sébastien Lalanne, Claire Fougerou-Leurent, George M. Anderson, Carmen M. Schroder, Tali Nir, Sylvie Chokron, Richard Delorme, Bruno Claustrat, Eric Bellissant, Solenn Kermarrec, Patricia Franco, Laure Denis and Sylvie Tordjman
Int. J. Mol. Sci. 2021, 22(3), 1490; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031490 - 02 Feb 2021
Cited by 41 | Viewed by 8802
Abstract
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 [...] Read more.
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. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments. Full article
(This article belongs to the Special Issue Melatonin: Lessons from Animals to Plants. Experimental and Clinical Studies)
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