Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(5), P. 2623 - 2633

Published: Jan. 11, 2024

Abstract This study utilized middle cerebral artery occlusion (MCAO) mouse models and HT‐22 cell oxygen glucose deprivation/reoxygenation (OGD/R) to investigate the therapeutic effects of melatonin on ischemic brain injury. In experiments, MCAO mice were treated with 5 10 mg/kg doses melatonin, H‐T22 cells underwent OGD/R treatment administered different concentrations melatonin. The results showed that significantly reduced area, neural damage, edema, neuronal apoptosis in mice. model, also improved proliferation ability, apoptosis, ROS production. Further mechanistic studies found exerts protective by inhibiting ferroptosis, an iron‐dependent form regulated death, through regulation ACSL4/CYP1B1 pathway. mice, decreased lipid peroxidation, production, ACSL4 protein expression. Overexpression CYP1B1 increased ubiquitination degradation, thereby increasing tolerance reducing levels, decreasing knockdown obtained opposite results. metabolite 20‐HETE induces expression E3 ubiquitin ligase FBXO10 activating PKC signaling, which promotes degradation. inhibition reversed summary, this demonstrates protects from injury ferroptosis pathway, providing evidence for new targets

Language: Английский

---

Mechanisms of inflammation after ischemic stroke in brain-peripheral crosstalk

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: June 12, 2024

Stroke is a devastating disease with high morbidity, disability, and mortality, among which ischemic stroke more common. However, there still lack of effective methods to improve the prognosis reduce incidence its complications. At present, evidence that peripheral organs are involved in inflammatory response after stroke. Moreover, interaction between central inflammation includes activation resident immune cells, as well inflammation-related signaling pathways, all play an important role pathophysiology In this review, we discuss mechanisms stroke, interactions through circulatory pathways (such gut, heart, lung spleen) brain mediate regulate We also propose potential meningeal lymphatic vessels (MLVs)-cervical lymph nodes (CLNs) brain-peripheral crosstalk pathway addition, summarize anti-inflammatory drugs treatment

Language: Английский

---

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure

Life, Journal Year: 2024, Volume and Issue: 14(1), P. 88 - 88

Published: Jan. 5, 2024

Cardiovascular disease is the cause of physical infirmity and thousands deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms energy production metabolic processing. Additionally, inflammation accumulation non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces initiation progression atherosclerotic lesions, which are often basis coronary artery disease. The current review critically analyzes published data related experimental use melatonin forestall pathologies. Collectively, these studies document melatonin’s anti-atherosclerotic actions reducing LDL oxidation triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, proliferation invasion arterial smooth muscle cells into lesioned area, restricting ingrowth blood vessels from vasa vasorum, solidifying plaque cap reduce chance its rupture. Diabetic hyperglycemia, aggravates also inhibited by supplementation animals. potential value non-toxic as a possible inhibitor pathology humans should be seriously considered performing clinical trials using this multifunctional molecule.

Language: Английский

---

Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation

Stroke and Vascular Neurology, Journal Year: 2025, Volume and Issue: unknown, P. svn - 003442

Published: Feb. 24, 2025

Background Melatonin protects against ischaemic stroke in diabetic animal models, though the mechanisms involving brain and peripheral immune responses remain underexplored. We aimed to clarify how melatonin interacts with these protect mice. Methods Type 1 diabetes mellitus (T1DM) was induced mice using streptozotocin. RNA sequencing of tissue blood mononuclear cells (PBMCs) performed 24 hours poststroke. Inflammatory were evaluated 72 after ischaemia/reperfusion. Results reduced infarction improved neurological function T1DM In brain, downregulated inflammatory factor expression, bioinformatics identifying 62 differentially expressed genes (DEGs) related inflammation 11 associated inflammasomes. Western blotting confirmed reductions NLRP3, HMGB1 Cleaved Caspase-1 expression. Flow cytometry showed infiltration CD8+T neutrophils. decreased IL-6, IL-1β IL-4 levels. PBMCs, revealed 939 DEGs following treatment. Kyoto Encyclopaedia Genes Genomes analysis indicated that involved metabolic pathways, upregulated enriched Jak-STAT signalling pathway. GO cytosol, macromolecule modification. Protein–protein interaction affected 38 inflammation-associated linked key cytokines (Il6, Il1b, Ifng, Il4). increased cells, monocytes neutrophils blood, suggesting a reversal immunosuppression. Multiplex cytokine assays IL-6 IFN-γ Conclusion Poststroke therapy reduces damage by modulating central responses.

Language: Английский

---

Mitochondrial Dynamics and Metabolism in Macrophages for Cardiovascular Disease: a review

Phytomedicine, Journal Year: 2025, Volume and Issue: 140, P. 156620 - 156620

Published: March 7, 2025

Language: Английский

---