Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment

Masters-Israilov, Alina; P, Seithikurippu R.; i-Perumal,; Seixas, Azizi; Jean-Louis, Girardin; McFarlane, Samy I.

doi:10.4172/2168-975x.1000151

Cited by 47 publications

(28 citation statements)

References 47 publications

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“…This observed effect of melatonin is intriguing, as the effect of melatonin on the permeability of vessels has been previously reported in the context of cancer and septic shock, and the function of melatonin has been attributed to Rho/ROCK pathway modulation and subsequent changes to the cytoskeletal elements including actin stress fibers (Borin et al., 2016, Tang et al., 2016). Melatonin has been proposed as a potential drug for Ebola hemorrhagic shock (Masters et al, 2014, Tan et al., 2014, Wiwanitkit, 2014) but has never been tested experimentally. Given that melatonin is a natural molecule in the body and is safe when administered for at least a year (Chahbouni et al., 2010) and given our observation that melatonin effectively suppresses the Ebola-induced loss of vascular integrity, our study suggests that melatonin is a promising drug for treating Ebola hemorrhagic shock syndrome.…”

Section: Resultsmentioning

confidence: 99%

Ebola Hemorrhagic Shock Syndrome-on-a-Chip

et al. 2020

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Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models for Ebola hemorrhagic fever is a major obstacle that hinders the development of treatment strategies. Here, we model the Ebola hemorrhagic syndrome in a microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion of Ebola virus-like particles leads to albumin leakage from the engineered vessels. The process is mediated by the Rho/ROCK pathway and is associated with cytoskeleton remodeling. Infusion of Ebola glycoprotein (GP 1,2) generates a similar phenotype, indicating the key role of GP 1,2 in this process. Finally, we measured the potency of a recently developed experimental drug FX06 and a novel drug candidate, melatonin, in phenotypic rescue. Our study confirms the effects of FX06 and identifies melatonin as an effective, safe, inexpensive therapeutic option that is worth investigating in animal models and human trials.

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Section: Resultsmentioning

confidence: 99%

Ebola Hemorrhagic Shock Syndrome-on-a-Chip

et al. 2020

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“…The next two steps include the conversion of serotonin to N ‐acetylserotonin by serotonin N ‐acetyltransferase followed by the conversion of N ‐acetylserotonin to MEL by hydroxyl‐indole‐ O ‐methyltransferase (Fernández‐Cruz, Álvarez‐Fernández, Valero, Troncoso, & García‐Parrilla, 2017). When the pineal gland receives input from postganglionic fibers, noradrenaline is released and production of cyclic adenosine monophosphate is increased, thus activating the enzyme serotonin N ‐acetyltransferase (Seithikurippu, 2015). The activity of the enzymes tryptophan hydroxylase and serotonin N ‐acetyltransferase in the pineal gland is regulated by the intensity of innervation by the axons of the suprachiasmatic nuclei, that is, signals carrying internal information about the photoperiod, beta‐ and, to a lesser extent, alpha‐adrenergic receptors on the surface of pinealocytes, and determining the amount of synthesized MEL.…”

Section: Origin and Physiological Functions Of Melatoninmentioning

confidence: 99%

Naturally occurring melatonin: Sources and possible ways of its biosynthesis

Juhnevica-Radenkova

Moreno

Ikase

et al. 2020

Comp Rev Food Sci Food Safe

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According to recent reports, the global market for melatonin is worth 700 million USD in 2018 and would reach 2,790 million USD by 2025, growing at a CAGR of 18.9% during 2019 to 2025. Having regard to the prevalence of sleep and circadian rhythm disorders and a clear tendency to increase the demand for melatonin, and the current lack of alternative green and cost-efficient technologies of its synthesis, the supply of this remedy will not be enough to guarantee melatonin supply and affordability on a global scale. The emergence of naturally occurring melatonin and its isomers in fermented foods has opened an exciting new research area; there are still, however, some obscure points in the efficient microbiological biosynthesis of melatonin. This review summarizes the research progress and recent evidence related to melatonin and its isomers in various foodstuffs. Additionally, one possible way to synthesize melatonin is also discussed. The evidence pointed out that the presence of melatonin and its isomers is not exclusive for grapes and grape-derived products, because it can be also found in sweet and sour cherries. However, different species of both Saccharomyces and non-Saccharomyces yeasts could be used to obtain melatonin and melatonin isomers in the process of alcoholic fermentation biotechnologically. The availability of L-tryptophan has been a key factor in determining the concentration of indolic compounds produced, and the utilization of probiotic lactic acid bacteria could help in the formation of melatonin isomers during malolactic fermentation. These approaches are environmentally friendly alternatives with a safer profile than conventional ones and could represent the future for sustainable industrial-scale melatonin production. K E Y W O R D S alcoholic fermentation, cherry, melatonin, Saccharomyces, yeast 1 ORIGIN AND PHYSIOLOGICAL FUNCTIONS OF MELATONIN Melatonin (MEL), or N-acetyl-5-methoxytryptamine, is a hormone, an indolamine that predominantly appears in plants, microorganisms, and mammals. Primarily, MEL was studied as a neurohormone of the pineal gland, which was discovered for the first time by Lerner, Case, Takahashi, Lee, and Mori (1958). The precursor of this molecule is solely the amino acid L-tryptophan

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“…In the general population, melatonin plasma levels are lower during the day and higher at night, with maximum peak secretion occurring typically 3–4 h after falling asleep (8). Besides its role as a circadian regulator, melatonin also acts as a pleiotropic molecule, showing antioxidant, immunomodulatory, anti-inflammatory, and anti-coagulopathic properties (9). Melatonin also modulates neuronal networks by changing the circadian neuronal transmission via direct effect of MT1 and MT2 synaptic receptors (10–14).…”

Section: Introductionmentioning

confidence: 99%

Morning Plasma Melatonin Differences in Autism: Beyond the Impact of Pineal Gland Volume

et al. 2019

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While low plasma melatonin, a neuro-hormone synthesized in the pineal gland, has been frequently associated with autism, our understanding of the mechanisms behind it have remained unclear. In this exploratory study, we hypothesized that low melatonin levels in ASD could be linked to a decrease of the pineal gland volume (PGV). PGV estimates with magnetic resonance imaging (MRI) with a voxel-based volumetric measurement method and early morning plasma melatonin levels were evaluated for 215 participants, including 78 individuals with ASD, 90 unaffected relatives, and 47 controls. We first found that both early morning melatonin level and PGV were lower in patients compared to controls. We secondly built a linear model and observed that plasma melatonin was correlated to the group of the participant, but also to the PGV. To further understand the relationship between PGV and melatonin, we generated a normative model of the PGV relationship with melatonin level based on control participant data. We found an effect of PGV on normalized melatonin levels in ASD. Melatonin deficit appeared however more related to the group of the subject. Thus, melatonin variations in ASD could be mainly driven by melatonin pathway dysregulation.

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Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment

Cited by 47 publications

References 47 publications

Ebola Hemorrhagic Shock Syndrome-on-a-Chip

Ebola Hemorrhagic Shock Syndrome-on-a-Chip

Naturally occurring melatonin: Sources and possible ways of its biosynthesis

Morning Plasma Melatonin Differences in Autism: Beyond the Impact of Pineal Gland Volume

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