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Vitamin D, Melatonin and Their Precursors in Natural Product

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: closed (15 October 2023) | Viewed by 4979

Special Issue Editors


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Guest Editor
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Interests: keratinocytes; vitamin D; melanoma; metabolism; skin biology; cell culture
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D and melatonin both act as anti-oxidative, anti-inflammatory and anti-cancer molecules in addition to their well-known roles in bone health and the regulation of circadian rhythm. Vitamins D3 and D2 are products of a photothermal transformation that occurs after the UVB absorption of the B ring of 7-dehydrocholesterol. Vitamin D is not only produced in vertebrates but also by invertebrates, fungi and plants.  In living organisms it is activated by series of hydroxylations in the canonical and non-canonical pathways. Melatonin and its precursor serotonin are synthesized and metabolized into biologically active products in most biological systems, including bacteria, eucarya, unicellular and multicellular fungi, plants and animals, including simple and complex vertebrates as well as invertebrates, indicating that these molecules are present in natural products. For example, they are detected in honey. Vitamin D and its derivatives are also present in natural products, since they have been detected in plants, fungi, insects and in honey. The implications for health, physiology and pathology are numerous.

The aim of this Special Issue, “Vitamin D, Melatonin and Their Precursors in Natural Products”, is to discuss natural products as sources of vitamin D, melatonin, its precursors, including serotonin, and its indolic and kynuric metabolites. Authors are invited to submit original research and review articles related to these subjects. Papers discussing the role of these compounds in health and diseases in human and non-human organisms will also be considered.

Prof. Dr. Andrzej Slominski
Dr. Tae-Kang Kim
Guest Editors

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Keywords

  • melatonin
  • serotonin
  • N-acetylserotonin
  • AFMK
  • AMK
  • vitamin D3
  • vitamin D2
  • hydroxyderivatives of vitamin D
  • natural products

Published Papers (2 papers)

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Research

19 pages, 6161 KiB  
Article
Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma
by Andrzej T. Slominski, Tae-Kang Kim, Radomir M. Slominski, Yuwei Song, Shariq Qayyum, Wojciech Placha, Zorica Janjetovic, Konrad Kleszczyński, Venkatram Atigadda, Yuhua Song, Chander Raman, Cornelis J. Elferink, Judith Varady Hobrath, Anton M. Jetten and Russel J. Reiter
Int. J. Mol. Sci. 2023, 24(20), 15496; https://doi.org/10.3390/ijms242015496 - 23 Oct 2023
Cited by 7 | Viewed by 1497
Abstract
Melatonin is widely present in Nature. It has pleiotropic activities, in part mediated by interactions with high-affinity G-protein-coupled melatonin type 1 and 2 (MT1 and MT2) receptors or under extreme conditions, e.g., ischemia/reperfusion. In pharmacological concentrations, it is given to counteract the massive [...] Read more.
Melatonin is widely present in Nature. It has pleiotropic activities, in part mediated by interactions with high-affinity G-protein-coupled melatonin type 1 and 2 (MT1 and MT2) receptors or under extreme conditions, e.g., ischemia/reperfusion. In pharmacological concentrations, it is given to counteract the massive damage caused by MT1- and MT2-independent mechanisms. The aryl hydrocarbon receptor (AhR) is a perfect candidate for mediating the latter effects because melatonin has structural similarity to its natural ligands, including tryptophan metabolites and indolic compounds. Using a cell-based Human AhR Reporter Assay System, we demonstrated that melatonin and its indolic and kynuric metabolites act as agonists on the AhR with EC50’s between 10−4 and 10−6 M. This was further validated via the stimulation of the transcriptional activation of the CYP1A1 promoter. Furthermore, melatonin and its metabolites stimulated AhR translocation from the cytoplasm to the nucleus in human keratinocytes, as demonstrated by ImageStream II cytometry and Western blot (WB) analyses of cytoplasmic and nuclear fractions of human keratinocytes. These functional analyses are supported by in silico analyses. We also investigated the peroxisome proliferator-activated receptor (PPAR)γ as a potential target for melatonin and metabolites bioregulation. The binding studies using a TR-TFRET kit to assay the interaction of the ligand with the ligand-binding domain (LBD) of the PPARγ showed agonistic activities of melatonin, 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynuramine with EC50’s in the 10−4 M range showing significantly lower affinities that those of rosiglitazone, e.g., a 10−8 M range. These interactions were substantiated by stimulation of the luciferase activity of the construct containing PPARE by melatonin and its metabolites at 10−4 M. As confirmed by the functional assays, binding mode predictions using a homology model of the AhR and a crystal structure of the PPARγ suggest that melatonin and its metabolites, including 6-hydroxymelatonin, 5-methoxytryptamine and N-acetyl-N-formyl-5-methoxykynuramine, are excellent candidates to act on the AhR and PPARγ with docking scores comparable to their corresponding natural ligands. Melatonin and its metabolites were modeled into the same ligand-binding pockets (LBDs) as their natural ligands. Thus, functional assays supported by molecular modeling have shown that melatonin and its indolic and kynuric metabolites can act as agonists on the AhR and they can interact with the PPARγ at high concentrations. This provides a mechanistic explanation for previously reported cytoprotective actions of melatonin and its metabolites that require high local concentrations of the ligands to reduce cellular damage under elevated oxidative stress conditions. It also identifies these compounds as therapeutic agents to be used at pharmacological doses in the prevention or therapy of skin diseases. Full article
(This article belongs to the Special Issue Vitamin D, Melatonin and Their Precursors in Natural Product)
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18 pages, 5028 KiB  
Article
Gardenia jasminoides Extract, with a Melatonin-like Activity, Protects against Digital Stress and Reverses Signs of Aging
by Morgane De Tollenaere, Emilie Chapuis, Jessy Martinez, Chantal Paulus, Joran Dupont, Eglantine Don Simoni, Patrick Robe, Bénédicte Sennelier-Portet, Daniel Auriol, Amandine Scandolera and Romain Reynaud
Int. J. Mol. Sci. 2023, 24(5), 4948; https://doi.org/10.3390/ijms24054948 - 03 Mar 2023
Cited by 2 | Viewed by 2566
Abstract
Digital stress is a newly identified cosmetic stress that is mainly characterized by blue light exposure. The effects of this stress have become increasingly important with the emergence of personal digital devices, and its deleterious effects on the body are now well-known. Blue [...] Read more.
Digital stress is a newly identified cosmetic stress that is mainly characterized by blue light exposure. The effects of this stress have become increasingly important with the emergence of personal digital devices, and its deleterious effects on the body are now well-known. Blue light has been observed to cause perturbation of the natural melatonin cycle and skin damage similar to that from UVA exposure, thus leading to premature aging. “A melatonin-like ingredient” was discovered in the extract of Gardenia jasminoides, which acts as a filter against blue light and as a melatonin-like ingredient to prevent and stop premature aging. The extract showed significant protective effects on the mitochondrial network of primary fibroblasts, a significant decrease of −86% in oxidized proteins on skin explants, and preservation of the natural melatonin cycle in the co-cultures of sensory neurons and keratinocytes. Upon analysis using in silico methods, only the crocetin form, released through skin microbiota activation, was found to act as a melatonin-like molecule by interacting with the MT1-receptor, thus confirming its melatonin-like properties. Finally, clinical studies revealed a significant decrease in wrinkle number of −21% in comparison to the placebo. The extract showed strong protection against blue light damage and the prevention of premature aging through its melatonin-like properties. Full article
(This article belongs to the Special Issue Vitamin D, Melatonin and Their Precursors in Natural Product)
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