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Melatonin Treatment in Diseases: From Clinical Application Research to Targeted Drug

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

Deadline for manuscript submissions: 20 July 2025 | Viewed by 1317

Special Issue Editor

Special Issue Information

Dear Colleagues,

Melatonin, or N-acetyl-5-methoxytryptamine, was discovered by Aaron B. Lerner, in 1958, during a study on the treatment of skin pigmentation diseases. Accumulating evidence points to several important roles of this indolamine, which is produced in the pineal gland and in many mammalian organs, including but not limited to the retina, gastrointestinal, cardiovascular, and reproductive systems. It acts as a regulatory molecule of the daily light and dark cycle for the body and human functions. It also participates in free radical detoxification, bone formation, reproduction, and the regulation of body mass; it also has an influence on cardiovascular, respiratory, urinary, and neurological homeostasis. In addition, antihypertensive, oncostatic, antioxidant, and anti-aging effects of melatonin have been identified, which could provide new insight into therapeutic strategies for various diseases. These peculiar therapeutic effects result from a variety of mechanisms of action that take place in various cellular compartments, including the cytoplasm, mitochondria, and nucleus, as well as in the extracellular matrix.

Melatonin is known to act with MT1 and MT2 receptors in cell membranes, but it diffuses passively across biological membranes due to its low molecular weight (232.3 Da), lipophilicity, and ionization at acid/base equilibrium. Therefore, it has a direct and indirect influence on many diseases. First, it maintains the proper quality of sleep regulation; sleep disorders lead to depression and behavioral complications. Sleep deficiency is linked to physical weakness, increased aggression, and altered disorders. Moreover, abnormalities in melatonin production or secretion are linked to pathologies of many systems. Oral and topical uses should be better evaluated in clinical trials to determine and define the effects of melatonin.

This Special Issue on “Melatonin Treatment in Diseases: From Clinical Application Research to Targeted Drug” will include manuscripts representing recent advances in therapeutic approaches for many diseases in the field of melatonin. Papers that aim to improve our understanding of the effects of this indolamine and its signaling pathways are welcome. Original research and reviews on these and related topics, such as ongoing and completed clinical trials, are invited.

Prof. Dr. Rita Rezzani
Guest Editor

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Keywords

  • health and pathology
  • oxidative stress and inflammation
  • endothelial dysfunction
  • aging and cancer
  • skin diseases
  • gastrointestinal disorders
  • neurodegenerative and cardiovascular diseases
  • microbiota composition and function
  • brain-gut axis
  • metabolic syndromes
  • sex/gender dimorphism

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Published Papers (1 paper)

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21 pages, 1942 KiB  
Article
Daily Lipolysis Gene Expression in Male Rat Mesenteric Adipose Tissue: Obesity and Melatonin Effects
by Pilar Cano-Barquilla, Vanesa Jiménez-Ortega, Pilar Fernández-Mateos, Leire Virto, Estela Maldonado Bautista, Juliana Perez-Miguelsanz and Ana I. Esquifino
Int. J. Mol. Sci. 2025, 26(2), 577; https://doi.org/10.3390/ijms26020577 - 11 Jan 2025
Viewed by 880
Abstract
Melatonin is involved in various functions such as the timing of circadian rhythms, energy metabolism, and body mass gain in experimental animals. However, its effects on adipose tissue lipid metabolism are still unclear. This study analyzes the effects of melatonin on the relative [...] Read more.
Melatonin is involved in various functions such as the timing of circadian rhythms, energy metabolism, and body mass gain in experimental animals. However, its effects on adipose tissue lipid metabolism are still unclear. This study analyzes the effects of melatonin on the relative gene expression of lipolytic proteins in rat mesenteric adipose tissue and free fatty acid (FFA) and glycerol plasma levels of male Wistar rats fed a high-fat (HFD) or maintenance diet. Four experimental groups were established: control, obese, and control or obese plus 2.3 mg/kg/day of melatonin in tap water. After 11 weeks, animals were sacrificed at different times throughout a 24 h cycle, and mesenteric adipose tissue and plasma samples were collected and analyzed. Cgi58, Perilipin, and Dgat1 gene expression, as well as FFA and glycerol concentrations, showed rhythm patterns in the control group. HFD disrupted those rhythm patterns and increased FFA and glycerol concentrations during the dark photoperiod. In both melatonin-treated groups, almost all analyzed genes showed circadian patterns. Notably, melatonin significantly prevented the increase in FFA levels during the dark photoperiod in obese rats (obese group: ~1100 mM vs. obese + melatonin group: ~600 μM, similar to control levels). However, the rhythmic pattern observed in control animals was not sustained. According to our results, melatonin could regulate circadian gene transcription of mesenteric adipose tissue lipolysis proteins. The effect of melatonin on preventing elevated FFA plasma levels associated with high-fat diet intake warrants further investigation. Full article
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