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Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease
Open accessAbstract
There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.
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![Figure 1 The roles of melatonin within the mitochondria. Melatonin is transported into mitochondria through PEPT1/2 oligopeptide and Glut/SLC2A transporters, but it is also synthesized within mitochondria [12,13]. Melatonin lowers the formation of free radicals and protects ATP synthesis at the mitochondrial level. It scavenges free oxygen (ROS) and nitrogen (RNS) reactive species, by preventing mitochondrial apoptosis and disruption of the electron transport chain. Melatonin interacts with MT1 and MT2 melatonin receptors, inhibits pro-apoptosis protein synthesis, and the subsequently cytochrome C leakage at the level of the membrane. It also protects mitochondrial DNA and prevents the opening of the mitochondrial permeability transition pore (mPTP) [13].](/paper-figures/3c708f53582d489aad2dd6daaeedb0a8/melatonins-impact-on-antioxidative-and-anti-inflammatory-reprogramming-in-figure-1.jpg)
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In the citing paper
“Melatonin interferes with inflammatory processes by interacting with cyclooxygenase (COX2), which is a key mediator of inflammatory processes and promotes apoptosis in malignant cells (Favero et al. 2017; Chitimus et al. 2020).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Chitimus et al. 2020
In the citing paper
“Melatonin’s dual actions can inhibit pro-oxidative enzymes (e.g., xanthine oxidase) while also acting to potentiate the critical antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase, and catalase, aiding in the body’s first line of immune defense and metabolic detoxification [31,32].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“Low levels of melatonin may trigger an upregulation in the kynurenine pathway, and kynurenine production, as well as trigger the aryl hydrocarbon receptor (AhR) located on the outer membrane of the mitochondria [32,55,56,57,58].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“Conversely, acute or chronic inflammation and stress have been found to increase the throughput of the kynurenine pathway, leading to an increase in tryptophan’s conversion to kynurenine [32,55].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“When AhR is triggered, overall endogenous pineal melatonin production is suppressed [32,55,56,57,58].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“High concentration levels of kynurenine in the brain are present in instances of depression [32,55].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“The melatonin-serotonin pathway accounts for approximately five percent of dietary tryptophan degradation, while the kynurenic pathway accounts for approximately 95 percent of dietary tryptophan degradation [32,56].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“Melatonin is derived from serotonin using 5-hydroxytryptophan (5-HTP) and tryptophan [32,55].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
In the citing paper
“Quinolinic acid is a neurotoxin, while kynurenic acid has neuroprotective properties [32,55,56,57,58].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [32]
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Metadata
- Authors
- Chitimus, D. M., Popescu, M. R., Voiculescu, S. E., Panaitescu, A. M., Pavel, B., Zagrean, L., & Zagrean, A.-M.
- Affiliations
- Division of Physiology and Neuroscience, Department of Functional Sciences, “Carol Davila” University of Medicine and Pharmacy, 010164 Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy (RO)
- ORCID
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2020-08-20
- Volume
- 10
- Issue
- 9
- Pages
- 1211
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7563541
- OpenAlex
- W3058036789
- Semantic Scholar
- 262cbe3526edc06c7fcb8c018bdcb2a802d687a3
- Cited by
- 354
- References
- 223
- Citations by year
- 2026: 52 · 2025: 85 · 2024: 70 · 2023: 65 · 2022: 53 · 2021: 26 · 2020: 2
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, antioxidant activity, anti-inflammatory activity, oxidative stress, inflammation, allostasis, pregnancy, offspring survival, hypertension, myocardial ischemia-reperfusion injury, cardiovascular disease, metabolic syndrome, neurodegenerative diseases, COVID-19 treatment, melatonin supplementation
- MeSH terms
- COVID-19, Adjuvants, Pharmaceutic, Animals, Anti-Inflammatory Agents, Antioxidants, Homeostasis, Humans, Melatonin, Pneumonia, Viral, Coronavirus Infections, Pandemics
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