Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.
Phytomedicine
; 132: 155877, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39032283
ABSTRACT
BACKGROUND:
White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models.OBJECTIVES:
To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model.METHODS:
The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis.RESULTS:
GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM.CONCLUSION:
This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dementia, Vascular
/
Oxidative Stress
/
Neuroprotective Agents
/
Disease Models, Animal
/
Cognitive Dysfunction
/
White Matter
Limits:
Animals
Language:
En
Journal:
Phytomedicine
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2024
Document type:
Article
Country of publication:
Germany