Key Components of PPEO in Antagonizing Cerebral Ischemic Reperfusion Injury in Rats by Regulating Ferroptosis Through Arachidonic Acid Metabolic Pathway
Zilong Du, Fan Huang, Yilin Liang, Lu Xie, Wanxiang Hu
TL;DR
This study identifies Nootkatone in Pomelo peel essential oil as a potential treatment for brain injury after stroke by targeting a specific fatty acid pathway.
Contribution
Nootkatone is shown to antagonize ferroptosis in global cerebral ischemic reperfusion injury through the AA metabolic pathway.
Findings
Nootkatone and β-pinene improved neuronal morphology and increased GPX4 levels in CIRI models.
Nootkatone exhibited strong binding to ALOX15 and reduced lipid metabolic disturbances in the CA/CPR model.
AA metabolism is ferroptosis-associated in global CIRI and inflammation-driven in focal CIRI.
Abstract
Cerebral ischemic reperfusion injury (CIRI) induces irreversible neurological dysfunction with high morbidity and mortality, yet effective clinical interventions remain limited. This study focused on ferroptosis in CIRI and explored the neuroprotective components and mechanisms of Pomelo peel essential oil (PPEO)—a product derived from Guangxi’s characteristic Shatian pomelo. Sprague-Dawley rats were used to establish two CIRI models: focal CIRI via Middle Cerebral Artery Occlusion (MCAO) and global CIRI via Cardiac Arrest/Cardiopulmonary Resuscitation (CA/CPR). Analyses were conducted using metabolomics, transcriptomics, histopathological staining, biochemical assays, RT-qPCR, Western blotting (WB), and molecular docking. Metabolomic results showed altered lipid-related metabolites in both models, predominantly unsaturated fatty acids and components of the arachidonic acid (AA)…
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Taxonomy
TopicsFerroptosis and cancer prognosis · Inflammasome and immune disorders · Cholesterol and Lipid Metabolism