Dauricine alleviated secondary brain injury after intracerebral hemorrhage by upregulating GPX4 expression and inhibiting ferroptosis of nerve cells.

Abstract

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high disability and mortality, and no effective treatment is available. Previous research on intracerebral hemorrhage secondary brain injury drugs mainly targeted at cell apoptosis, inflammation and oxidative stress, but did not achieve good effects. In recent years, ferroptosis has become a focus concern in neurological diseases. Ferroptosis is a new type of programmed cell death caused by iron-dependent accumulation of lipid peroxides, in which glutathione peroxidase 4 (GPX4) is a key protein affecting ferroptosis. In this study, we used the STRING protein database to predict the proteins that may be co-expressed with GPX4, and studied the ability of Dauricine(Dau) to up-regulate the expression of GPX4 against ferroptosis and neuroprotection after intracerebral hemorrhage in normal cells in vitro, glutathione peroxidase 4 (GPX4) knockdown cells and collagenase injection in vivo in mouse models of intracerebral hemorrhage. The results showed that glutathione reductase (GSR) was a possible co-expression protein with GPX4. Dau could up-regulate the expression of glutathione peroxidase 4 (GPX4) in intracerebral hemorrhage(ICH) model, normal cells and GPX4 knockdown cells in vitro, and simultaneously up-regulate the expression of GSR in ICH mice. Dau could also reduce the levels of iron and lipid peroxidation, and have a neuroprotective effect on intracerebral hemorrhage(ICH) mice. It was tesified that Dauricine(Dau) could inhibit ferroptosis of nerve cells and alleviate brain injury after intracerebral hemorrhage by upregulating glutathione peroxidase 4 (GPX4) and glutathione reductase (GSR) co-expression. Therefore, Dau may be an effective drug for inhibiting ferroptosis and treating intracerebral hemorrhage.

• Authors: Chiwei Peng, Xiang Fu, Kaixuan Wang, Ling Chen, Beijiao Luo, Ni Huang, Yunfeng Luo, Wei Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 914 Pg. 174461 (Jan 05 2022) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34469757 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Benzylisoquinolines
• Lipid Peroxides
• Neuroprotective Agents
• Tetrahydroisoquinolines
• dauricine
• Phospholipid Hydroperoxide Glutathione Peroxidase
• glutathione peroxidase 4, mouse
• Glutathione Reductase

Topics

• Animals
• Benzylisoquinolines (pharmacology)
• Cells, Cultured
• Cerebral Hemorrhage (drug therapy, metabolism)
• Disease Models, Animal
• Ferroptosis (drug effects, physiology)
• Gene Expression Regulation (drug effects)
• Glutathione Reductase (metabolism)
• Lipid Peroxides (metabolism)
• Mice
• Mice, Knockout
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Phospholipid Hydroperoxide Glutathione Peroxidase (metabolism)
• Regulated Cell Death (drug effects, physiology)
• Tetrahydroisoquinolines (pharmacology)