Abstract

The objective of this study is to investigate the impact of melatonin on ischemic brain injury and elucidate its underlying molecular mechanism. In this investigation, a mouse model of middle cerebral artery occlusion (MCAO) was established using the thread occlusion method, followed by treatment with two different doses of melatonin: 5 mg/kg and 10 mg/kg. Additionally, HT-22 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and treated with varying concentrations of melatonin. The findings demonstrated that melatonin significantly reduced the extent of cerebral ischemia, nerve damage, brain edema, and neuronal apoptosis in MCAO mice. experiments further revealed that melatonin effectively enhanced cell proliferation while reducing cell apoptosis and reactive oxygen species (ROS) production following OGD/R treatment. Mechanistic investigations unveiled that melatonin exerted its protective effect by inhibiting ferroptosis through modulation of MDM2-mediated ubiquitination of ACSL4. In summary, this study suggests that melatonin regulates the MDM2/ACSL4 pathway to safeguard against ischemic brain injury, thereby providing novel therapeutic targets for such conditions.

MeSH

Stroke, Brain Injuries, Apoptosis, Aging, Cells, Therapeutics, Melatonin, Ubiquitination

Cited by

• Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer. Front Oncol, 2025
• Targeting ferroptosis with natural products in stroke: therapeutic mechanisms and translational opportunities. Front Pharmacol, 2025
• Ubiquitin-specific peptidase 14 promotes neuron injury by stabilizing acyl-CoA synthetase long-chain family member 4 through deubiquitination. Cytojournal, 2025
• Effects of the combination of melatonin and N-acetylcysteine on the inflammatory response in a rat model of cerebral ischemia. IBRO Neurosci Rep, 2025
• The role of ACSL4 in stroke: mechanisms and potential therapeutic target. Mol Cell Biochem, 2025