Is Melatonin the Cornucopia of the 21st Century?

Ferlazzo, Nadia; Andolina, Giulia; Cannata, Attilio; Costanzo, Maria Giovanna; Rizzo, Valentina; Currò, Monica; Ientile, Riccardo; Caccamo, Daniela

doi:10.3390/antiox9111088

Cited by 113 publications

(92 citation statements)

References 213 publications

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“…9,10,39 On the other hand, although melatonin is considered safer than BZD or zdrugs, its long-term effects have not been fully explored. 40 Lastly, despite declining trends in overall BZD and z-dug prescriptions, the increasing proportion of them provided to patients with an insomnia diagnosis is concerning, as it could increase the likelihood of dependence. Our findings are consistent with the reported rise in the prevalence of sleep issues in Australia during the past decade.…”

Section: Comparison With Existing Literaturementioning

confidence: 99%

Trends in the prescription of drugs used for insomnia: an open-cohort study in Australian general practice, 2011–2018

et al. 2021

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Background: Despite an increase in the prevalence of sleep problems, few studies have investigated changes in the prescribing of drugs often used for managing insomnia. Aim: To explore changes in the pattern of benzodiazepine (BZD), z-drugs (zolpidem, zopiclone) and non-BZD prescriptions. Design and Setting: Open cohort study including 1,773,525 patients (55,903,294 consultations) regularly attending 404 Australian general practices from 2011-2018 (MedicineInsight). Method: Prescription rates per 1,000 consultations, the proportion of repeat prescriptions above recommendations, and the proportion of prescriptions for patients with a recent recorded insomnia diagnosis (i.e. within 2 years) were analysed using adjusted regression models. Results: Rates of BZD, z-drugs and non-BZD prescriptions were 56.6, 4.4 and 15.5/1,000 consultations in 2011 and 41.8, 3.5 and 21.5/1000 consultations in 2018, respectively. Temazepam represented 25.3% of the prescriptions and diazepam 21.9%. All BZD and zolpidem prescriptions declined from 2011-2018 [annual change varying from -1.4% to -10.8%], while non-BZD and zopiclone prescriptions increased in the same period [annual change: +5.0% to +22.6%]. Repeat prescriptions above recommendations remained below 10% for most medications, except melatonin (64.5%), zolpidem (63.3%), zopiclone (31.4%) and alprazolam (13.3%). In 2018, almost 50% of z-drugs and melatonin prescriptions were for patients with insomnia. There was 3.2%-5.9% annual increase in the proportion of prescriptions associated with a recently recorded insomnia diagnosis. Conclusion: Overall, BZD prescriptions in Australia declined from 2011-2018. However, the prescription of some of these drugs increased for patients with a recently recorded insomnia diagnosis. This is concerning because of potential adverse effects and risk of dependence.

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Section: Comparison With Existing Literaturementioning

confidence: 99%

Trends in the prescription of drugs used for insomnia: an open-cohort study in Australian general practice, 2011–2018

et al. 2021

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“…Apart from the antioxidative effects, MT has a bundle of means whereby it thwarts intracellular damage through activating effectors downstream of MT receptors [ 59 ]. Previous studies have found that melatonin receptors mainly consist of membrane receptors (MTNR1A, MTNR1B) and nuclear receptors (RZR/ROR, retinoid Z receptor/retinoid acid receptor related orphan receptor) [ 60 ]. In ovarian follicles, it has been demonstrated that MT mediated the proliferation, apoptosis, and steroidogenesis of GCs predominantly through the activation of MTNR1B [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Alleviates Hypoxia-Induced Apoptosis of Granulosa Cells by Reducing ROS and Activating MTNR1B–PKA–Caspase8/9 Pathway

et al. 2021

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In mammalian ovaries, the avascular environment within follicular cavity is supposed to cause hypoxic status in granulosa cells (GCs), leading to apoptotic cell death accompanied by cumulative reactive oxygen species (ROS) production. Melatonin (N-acetyl-5-methoxytryptamine, MT), a broad-spectrum antioxidant that exists in porcine follicle fluid, was suggested to maintain GCs survival under stress conditions. In this study, using the established hypoxic model (1% O2) of cultured porcine GCs, we explored the effect of MT on GCs apoptosis. The results showed that MT restored cell viability and reduced the apoptosis of GCs during hypoxia exposure. In addition, GCs treated with MT exhibited decreased ROS levels and increased expression of antioxidant enzymes including heme oxygenase-1 (HO-1), glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and catalase (CAT) upon hypoxia incubation. Moreover, the hypoxia-induced expression of cleaved caspase 3, 8, and 9 was significantly inhibited after MT treatment. In contrast, blocking melatonin receptor 2 (MTNR1B) with a competitive antagonist 4-phenyl-2-propionamidotetralin (4P-PDOT) diminished the inhibitory effects of MT on caspase 3 activation. By detecting levels of protein kinase (PKA), a downstream kinase of MTNR1B, we further confirmed the involvement of MT–MTNR1B signaling in mediating GCs protection during hypoxia stress. Together, the present data provide mechanistic evidence suggesting the role of MT in defending GCs from hypoxia-induced apoptosis.

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“…Melatonin exerts a potent immunomodulatory activity in vivo and in vitro [177][178][179]. Melatonin membrane receptors are present in T and B lymphocytes [69].…”

Section: Immunomodulatory Effects Of Melatoninmentioning

confidence: 99%

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

Kopustinskienė

Bernatonienė

2021

Pharmaceutics

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Melatonin, an endogenously synthesized indolamine, is a powerful antioxidant exerting beneficial action in many pathological conditions. Melatonin protects from oxidative stress in ischemic/reperfusion injury, neurodegenerative diseases, and aging, decreases inflammation, modulates the immune system, inhibits proliferation, counteracts the Warburg effect, and promotes apoptosis in various cancer models. Melatonin stimulates antioxidant enzymes in the cells, protects mitochondrial membrane phospholipids, especially cardiolipin, from oxidation thus preserving integrity of the membranes, affects mitochondrial membrane potential, stimulates activity of respiratory chain enzymes, and decreases the opening of mitochondrial permeability transition pore and cytochrome c release. This review will focus on the molecular mechanisms of melatonin effects in the cells during normal and pathological conditions and possible melatonin clinical applications.

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Is Melatonin the Cornucopia of the 21st Century?

Cited by 113 publications

References 213 publications

Trends in the prescription of drugs used for insomnia: an open-cohort study in Australian general practice, 2011–2018

Trends in the prescription of drugs used for insomnia: an open-cohort study in Australian general practice, 2011–2018

Melatonin Alleviates Hypoxia-Induced Apoptosis of Granulosa Cells by Reducing ROS and Activating MTNR1B–PKA–Caspase8/9 Pathway

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

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