Open Access

REVIEW

Melatonin as a Neuroprotective Agent in Ischemic Stroke: Mechanistic Insights Centralizing Mitochondria as a Potential Therapeutic Target

Mayuri Shukla¹, Soraya Boonmag², Parichart Boontem¹, Piyarat Govitrapong^1,*

1 Chulabhorn Graduate Institute, Kamphaeng Phet 6 Road, Lak Si, Bangkok, 10210, Thailand
2 Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand

* Corresponding Author: Piyarat Govitrapong. Email:

(This article belongs to the Special Issue: Melatonin and Mitochondria: Exploring New Frontiers)

BIOCELL 2026, 50(1), 4 https://doi.org/10.32604/biocell.2025.072557

Received 29 August 2025; Accepted 29 October 2025; Issue published 23 January 2026

Abstract

Ischemic stroke is one of the major causes of long-term disability and mortality worldwide. It results from an interruption in the cerebral blood flow, triggering a cascade of detrimental events like oxidative stress, mitochondrial dysfunction, neuroinflammation, excitotoxicity, and apoptosis, causing neuronal injury and cellular death. Melatonin, a pleiotropic indoleamine produced by the pineal gland, has multifaceted neuroprotective effects on stroke pathophysiology. Interestingly, the serum melatonin levels are associated with peroxidation and antioxidant status, along with mortality score in patients with severe middle cerebral artery infarction. Melatonin exhibits strong antioxidant, anti-inflammatory, and anti-apoptotic properties and preserves mitochondrial function and homeostasis. Several preclinical studies have shown that melatonin administration conserves blood-brain barrier integrity, reduces infarct size, and edema. These mechanisms contribute to minimizing tissue damage and improving the neurological outcomes following ischemic events. Therefore, the present review evaluates evidence from experimental studies furthered with limited clinical investigations and explores the mechanistic pathways of melatonin functions to establish its therapeutic potential in stroke management.

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Keywords

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