The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology
This work reviews the complex interplay between melatonin and nitric oxide (NO) in the central nervous system (CNS), with a detailed focus on its involvement in stroke pathophysiology. Melatonin, a neurohormone with potent antioxidant, anti-inflammatory, and neuroprotective properties, and NO, a gas...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/6/724 |
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| author | Santos Blanco María del Mar Muñoz-Gallardo Raquel Hernández María Ángeles Peinado |
| author_facet | Santos Blanco María del Mar Muñoz-Gallardo Raquel Hernández María Ángeles Peinado |
| author_sort | Santos Blanco |
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| description | This work reviews the complex interplay between melatonin and nitric oxide (NO) in the central nervous system (CNS), with a detailed focus on its involvement in stroke pathophysiology. Melatonin, a neurohormone with potent antioxidant, anti-inflammatory, and neuroprotective properties, and NO, a gaseous signaling molecule with diverse roles, interact crucially. In the context of ischemic stroke, NO exhibits a dual role: it can be neuroprotective (primarily via endothelial nitric oxide synthase (eNOS)) or neurotoxic (especially through inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), contributing to the formation of damaging peroxynitrite (ONOO<sup>−</sup>)). Melatonin has consistently demonstrated neuroprotective effects in animal models of stroke. Its key mechanisms related to NO include (1) differential modulation of nitric oxide synthase isoforms, suppressing detrimental iNOS expression/activity while often preserving or enhancing beneficial eNOS; (2) direct scavenging of NO and, critically, highly reactive peroxynitrite, thereby attenuating nitrosative stress; (3) reduction in neuroinflammation, partly by promoting M2 (anti-inflammatory) microglia polarization; and (4) mitochondrial protection and decreased apoptosis. These multifaceted actions of melatonin contribute to reduced infarct volume and improved functional outcomes, underscoring its considerable therapeutic potential for ischemic stroke through the favorable modulation of the melatonin–NO axis. |
| format | Article |
| id | doaj-art-de7e3e753ea0440193ed854ffbb7f796 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-de7e3e753ea0440193ed854ffbb7f7962025-08-20T03:26:09ZengMDPI AGAntioxidants2076-39212025-06-0114672410.3390/antiox14060724The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke PathophysiologySantos Blanco0María del Mar Muñoz-Gallardo1Raquel Hernández2María Ángeles Peinado3Department of Experimental Biology, University of Jaén, 23007 Jaén, SpainDepartment of Experimental Biology, University of Jaén, 23007 Jaén, SpainDepartment of Experimental Biology, University of Jaén, 23007 Jaén, SpainDepartment of Experimental Biology, University of Jaén, 23007 Jaén, SpainThis work reviews the complex interplay between melatonin and nitric oxide (NO) in the central nervous system (CNS), with a detailed focus on its involvement in stroke pathophysiology. Melatonin, a neurohormone with potent antioxidant, anti-inflammatory, and neuroprotective properties, and NO, a gaseous signaling molecule with diverse roles, interact crucially. In the context of ischemic stroke, NO exhibits a dual role: it can be neuroprotective (primarily via endothelial nitric oxide synthase (eNOS)) or neurotoxic (especially through inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), contributing to the formation of damaging peroxynitrite (ONOO<sup>−</sup>)). Melatonin has consistently demonstrated neuroprotective effects in animal models of stroke. Its key mechanisms related to NO include (1) differential modulation of nitric oxide synthase isoforms, suppressing detrimental iNOS expression/activity while often preserving or enhancing beneficial eNOS; (2) direct scavenging of NO and, critically, highly reactive peroxynitrite, thereby attenuating nitrosative stress; (3) reduction in neuroinflammation, partly by promoting M2 (anti-inflammatory) microglia polarization; and (4) mitochondrial protection and decreased apoptosis. These multifaceted actions of melatonin contribute to reduced infarct volume and improved functional outcomes, underscoring its considerable therapeutic potential for ischemic stroke through the favorable modulation of the melatonin–NO axis.https://www.mdpi.com/2076-3921/14/6/724melatoninnitric oxidestrokeCNSischemiamolecular mechanisms |
| spellingShingle | Santos Blanco María del Mar Muñoz-Gallardo Raquel Hernández María Ángeles Peinado The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology Antioxidants melatonin nitric oxide stroke CNS ischemia molecular mechanisms |
| title | The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology |
| title_full | The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology |
| title_fullStr | The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology |
| title_full_unstemmed | The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology |
| title_short | The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology |
| title_sort | interplay between melatonin and nitric oxide mechanisms and implications in stroke pathophysiology |
| topic | melatonin nitric oxide stroke CNS ischemia molecular mechanisms |
| url | https://www.mdpi.com/2076-3921/14/6/724 |
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