Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement

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国家科技期刊平台
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外文摘要：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.

外文关键词：

GLP-1R agonistDiabetesCognitive disorderMitophagyCell membrane chromatography

作者：

Na Liu、Xin Cui、Wenhui Yan、Tingli Guo、Zhuanzhuan Wang、Xiaotong Wei、Yuzhuo Sun、Jieyun Liu、Cheng Xian、Weina Ma、Lina Chen

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作者单位：

Department of Pharmacology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,China

Hezhou People's Hospital,Guangxi Zhuang Autonomous Region,Hezhou,Guangxi,542899,China

School of Pharmacy,Xi'an Jiaotong University Health Science Center,Xi'an,710061,China

Key Laboratory of Environment and Genes Related to Diseases(Xi'an Jiaotong University),Ministry of Education,Xi'an,710061,China

Cardiometabolic Innovation Center,Ministry of Education,Xi'an,710061,China

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出版年：

2024

DOI：

10.1016/j.jpha.2024.100968

药物分析学报(英文)

西安交通大学

药物分析学报(英文)

影响因子：0.244

ISSN：2095-1779

年,卷(期)：2024.14(8)