Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement
10.1016/j.jpha.2024.100968
- Author:
Liu NA
1
;
Cui XIN
;
Yan WENHUI
;
Guo TINGLI
;
Wang ZHUANZHUAN
;
Wei XIAOTONG
;
Sun YUZHUO
;
Liu JIEYUN
;
Xian CHENG
;
Ma WEINA
;
Chen LINA
Author Information
1. Department of Pharmacology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,China
- Keywords:
GLP-1R agonist;
Diabetes;
Cognitive disorder;
Mitophagy;
Cell membrane chromatography
- From:
Journal of Pharmaceutical Analysis
2024;14(8):1189-1204
- CountryChina
- Language:Chinese
-
Abstract:
There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
