“Background: Perinatal hypoxia-ischemia is a major cause of long-term neurological impairments in newborns, with ferroptosis recognized as a key mechanism of injury.
Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with antioxidant and neuroprotective properties.
CBD is a potential modulator of hypoxic-ischemic brain damage, however its effects on ferroptosis-related pathways remain unclear.
Purpose: In this study, we examined whether CBD can alleviate ferroptosis-associated damage in differentiated human neuroblastoma (neuron-like SH-SY5Y) cell model of hypoxic-ischemic injury.
Study design: Differentiated human neuroblastoma cells were exposed to oxygen-glucose deprivation (OGD) to simulate hypoxic-ischemic conditions.
Methods: Neuron-like SH-SY5Y cells were subjected to OGD to induce hypoxic-ischemic injury. CBD was applied to assess its neuroprotective effects. Oxidative stress markers, antioxidant enzyme activity, transcription factor activation Nrf2 (nuclear factor erythroid 2-related factor 2), iron metabolism proteins (ferroportin), hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression were evaluated.
Results: CBD application significantly reduced oxidative stress by improving antioxidant capacity and lowering total oxidant status. CBD also preserved the expression and enzymatic activity of glutathione peroxidase 4, a central enzyme protecting against lipid peroxidation, and enhanced the activation of Nrf2, a key regulator of antioxidant defence. Additionally, CBD prevented OGD-induced downregulation of ferroportin, potentially supporting iron efflux and reducing ferroptotic risk. HIF-1α and its downstream target VEGF were upregulated under hypoxic conditions, and CBD further enhanced VEGF expression.
Conclusion: CBD mitigates ferroptosis by modulating redox balance, antioxidant defence, and iron metabolism, supporting its potential role as a therapeutic strategy for neonatal hypoxic-ischemic brain injury.”
https://pubmed.ncbi.nlm.nih.gov/41581443
“These findings support the potential use of CBD as a therapeutic agent for hypoxia-related ferroptotic injury, such as neonatal hypoxic-ischemic encephalopathy.”
https://www.sciencedirect.com/science/article/abs/pii/S0944711326001078?via%3Dihub