2. Academic Validation
  3. Chrysin Improves Cognitive Dysfunction in Rats with Intracerebral Hemorrhage by Regulating the Nrf2/GPX4 Pathway to Inhibit Ferroptosis

Chrysin Improves Cognitive Dysfunction in Rats with Intracerebral Hemorrhage by Regulating the Nrf2/GPX4 Pathway to Inhibit Ferroptosis

  • Mol Neurobiol. 2025 Nov 13;63(1):35. doi: 10.1007/s12035-025-05335-0.
Dachuang Guo # 1 2,  Zhe Shao # 1 2,  Dayuan Liu # 3,  Yong Guan 1 2,  Dongye Lian 1 2,  Jigao Feng 4,  Caicai Zhang 5 6,  Hao Peng 7 8
Affiliations

Affiliations

  • 1 Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China.
  • 2 Department of Neurosurgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.
  • 3 Department of Neurosurgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
  • 4 Department of Neurosurgery, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China. [email protected].
  • 5 Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan, China. [email protected].
  • 6 Department of Physiology, Hainan Medical University, Haikou, Hainan, China. [email protected].
  • 7 Department of Neurosurgery, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China. [email protected].
  • 8 Department of Neurosurgery, The Second People's Hospital of Hainan Province, Wuzhishan, Hainan, China. [email protected].
  • # Contributed equally.
PMID: 41231360 DOI: 10.1007/s12035-025-05335-0
Abstract

Intracerebral hemorrhage (ICH) is a serious hemorrhagic stroke. Secondary nerve injury can cause nerve cell Ferroptosis (FER), which promotes oxidative stress and inflammatory response and has been associated with poor prognosis in patients. Chrysin (CHR) has various bioactivities, such as antioxidative stress, anti-inflammatory, anti-FER, and neuroprotective effects. However, the role and mechanism of CHR in ICH remain undetermined. Therefore, this study established the rat ICH model using an autologous blood injection to investigate the brain tissue and hippocampal neuron morphological changes via hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy. Furthermore, FER-related indicators were detected using a reagent kit and western blotting. Moreover, the Morris water maze test was carried out to assess the cognitive function of rats. The results indicated that CHR treatment significantly reduced FER, oxidative stress, inflammation, and nerve injury in the hippocampus of ICH rats and improved their cognitive function. In addition, ML385, the Nrf2 inhibitor, reversed the CHR-induced upregulation of the Nrf2/GPX4 signaling pathway and aggravated cognitive dysfunction in ICH rats. In conclusion, this study indicated that CHR inhibits FER by regulating the Nrf2/GPX4 signaling pathway to alleviate nerve injury and improve cognitive dysfunction in ICH rats. Therefore, CHR can be employed as a new strategy for treating ICH.

Keywords

Chrysin; Cognitive dysfunction; Ferroptosis; Intracerebral hemorrhage; Nrf2/GPX4.

Figures
Products